Published online Jun 26, 2020. doi: 10.12998/wjcc.v8.i12.2425
Peer-review started: December 31, 2019
First decision: April 1, 2020
Revised: May 20, 2020
Accepted: May 23, 2020
Article in press: May 23, 2020
Published online: June 26, 2020
Processing time: 176 Days and 6.7 Hours
Gastrointestinal (GI) cancer is one of the leading causes of cancer-related deaths worldwide. According to the Global Cancer Statistics, colorectal cancer is the second leading cause of cancer-related mortality, closely followed by gastric cancer (GC). Environmental, dietary, and lifestyle factors including cigarette smoking, alcohol intake, and genetics are the most important risk factors for GI cancer. Furthermore, infections caused by Helicobacter pylori are a major cause of GC initiation. Despite improvements in conventional therapies, including surgery, chemotherapy, and radiotherapy, the length or quality of life of patients with advanced GI cancer is still poor because of delayed diagnosis, recurrence and side effect. Resveratrol (3, 4, 5-trihydroxy-trans-stilbene; Res), a natural polyphenolic compound, reportedly has various pharmacologic functions including anti-oxidant, anti-inflammatory, anti-cancer, and cardioprotective functions. Many studies have demonstrated that Res also exerts a chemopreventive effect on GI cancer. Research investigating the anti-cancer mechanism of Res for the prevention and treatment of GI cancer has implicated multiple pathways including oxidative stress, cell proliferation, and apoptosis. Therefore, this paper provides a review of the function and molecular mechanisms of Res in the prevention and treatment of GI cancer.
Core tip: Gastrointestinal (GI) cancer is a serious disease that affects people late in their lives and represents a global health burden. Despite improvements in conventional therapies, including surgery, chemotherapy, and radiotherapy, the length or quality of life of patients with advanced GI cancer is still poor. Many studies have demonstrated that resveratrol also exerts a chemopreventive effect on GI cancer. In this review, we describe the function and molecular mechanisms of resveratrol in the prevention and treatment of GI cancer.
- Citation: Wang LY, Zhao S, Lv GJ, Ma XJ, Zhang JB. Mechanisms of resveratrol in the prevention and treatment of gastrointestinal cancer. World J Clin Cases 2020; 8(12): 2425-2437
- URL: https://www.wjgnet.com/2307-8960/full/v8/i12/2425.htm
- DOI: https://dx.doi.org/10.12998/wjcc.v8.i12.2425
Gastrointestinal (GI) cancer is one of the leading causes of cancer-related deaths worldwide and represents a global health burden. To date, most research attention has been directed towards the prevention of gastric cancer (GC) and colorectal cancer (CRC), the most common forms of GI cancer. According to Global Cancer Statistics[1], CRC is the second leading cause of cancer-related mortality, closely followed by GC. GC was responsible for more than one million new cancer cases in 2018 and an estimated 783000 deaths, which equates to 1 in every 12 deaths globally. More than 1.8 million new CRC cases and 881000 deaths were estimated to occur in 2018. Environmental, dietary, and lifestyle factors, as well as family history, are the most important risk factors for GI cancer. Despite improvements in current cancer therapies, including surgery, chemotherapy, and radiotherapy, the length or quality of life (QoL) of patients with advanced GI cancer is still poor because of delayed diagnosis, recurrence, and medication side effect[2-4]. Therefore, the identification of novel therapeutic strategies to enhance the therapeutic effect and survival rate of patients with GI cancer is urgently needed.
Recently, traditional medicines, which are derived from natural compounds, have been reported as promising therapeutic agents. In particular, flavonoids and polyphenols have been recognized as potential therapeutic agents for cancer. Resveratrol (3, 4, 5-trihydroxy-trans-stilbene; Res), a natural polyphenolic compound, is widely found in grapes, cranberries, peanuts, and red wine[5]. Previous reports have demonstrated that Res has various valuable pharmacological effects including anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-bacterial, and cardiovascular protective effects[6-9]. The anti-tumor effect of Res was first reported in 1997[9]. Since then, many studies have indicated that Res exerts a wide range of preventive and therapeutic actions against various types of cancer including lung, colorectal, gastric, breast, and liver cancers. Moreover, many studies have demonstrated that Res might also exert chemopreventive effects when combined with other chemotherapeutic drugs. To date, the various anti-cancer molecular mechanisms of Res in the prevention and treatment of GI cancer have implicated multiple pathways in its effects including oxidative stress, cell proliferation, and apoptosis[10].
In this review, we summarize the principal findings supporting the anti-tumor properties of Res and describe its molecular mechanisms in GI cancer, either as a preventive or a therapeutic agent.
Helicobacter pylori (H. pylori) infection in the stomach induces a mucosal inflammatory response, oxidative stress, and changes to cell proliferation, which lead to GC[11-13]. Almost 90% of new cases of noncardia GC are attributed to this bacterium[14-16]. There are several mechanisms thought to be involved in the association between H. pylori and GC[17-20]. First, H. pylori can induce inflammatory mediators such as interleukin-8 (IL-8), IL-6, and tumor necrosis factor-α (TNF-α)[16]. Among these mediators, IL-8 plays a crucial role in the host inflammatory response to H. pylori[21-24]. The upregulation of IL-8 in H. pylori infection may lead to the generation of free radicals, and the release of proteolytic enzymes from activated neutrophils ultimately affects mucosal integrity[25]. Second, H. pylori can induce oxidative stress and generate reactive oxygen species (ROS) in gastric epithelial cells, which can lead to altered epithelial proliferation and oxidative DNA damage[26]. When cells were pretreated with Res, both IL-8 secretion and H. pylori-stimulated ROS generation were suppressed[27]. Third, the gastric mucosal inflammation and damage caused by H. pylori infection are mediated by the overproduction of nitric oxide (NO), which is generated by inducible NO synthase (iNOS). Constant overproduction of NO may lead to DNA and tissue damage, ultimately increasing the risk of developing cancer[28]. Activation of the nuclear factor kappa B (NF-κB) signal transduction pathway is also an important event linked to tumorigenesis[29]. Res exerts significant effects against H. pylori-induced oxidative stress and inflammation by suppressing the expression levels of IL-8 and iNOS, blocking the activation of NF-κB, and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 pathway[30].
Cell proliferation plays an important role in the development of cancer. Cells acquire an increasing number of defects in key genes that enable persistent cell growth when the cells start to divide. Thus, compounds with anti-proliferative activities may be cancer chemopreventive[31]. Evidence suggests that Res can inhibit the proliferation of several transformed cells in culture[32-34]. Protein kinase C (PKC), which is associated with tumor suppression and cell proliferation[35,36], and mitogen-activated protein kinases (extracellular signal-regulated kinase 1 [ERK1] and ERK2), are regulated by growth factors controlling the proliferation of normal cells. Res inhibits the growth of gastric adenocarcinoma cells through a PKC-mediated mechanism[34] and the MEK1/2-ERK1/2-c-Jun signaling pathway[37]. Res also induces cell cycle arrest through regulation of the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/Akt (PTEN/PI3K/Akt) signaling pathway and the Wnt/β-catenin signal pathway[38]. Res lowers the expression of related proteins in signaling pathways such as cyclin D1 (an important protein related to the G0/G1 cell cycle)[38,39]. Additionally, Res exerts its anti-proliferative action by interfering with the action of endogenously produced reactive oxygen. Res effectively inhibits hydrogen peroxide-stimulated proliferation and superoxide generation[25].
Cancer cell invasion and metastasis are interconnected processes that involve cell proliferation, cell migration, cell adhesion, and proteolytic degeneration of tissue barriers[40]. GC exhibits high motility due to its strong invasion and metastasis ability. The hedgehog (Hh) signaling pathway plays an important role in vertebrate development, the homeostatic process, and tumorigenesis. Res suppresses invasion and metastasis via inhibition of the Hh signaling pathway and epithelial-mesenchymal transition (EMT), which is also associated with cancer metastasis and invasion. Res was found to produce decreased expression of GLI family zinc finger 1, a key component of the Hh signaling pathway, as well as decreased expression of Snail and N-cadherin and increased expression of E-cadherin, which are key components of the EMT[41]. In addition, Res can inhibit metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression[42].
IL-6 is a multifunctional cytokine that plays a vital role in host defense mechanisms and the growth of various cancer cells[43]. Yang found that Res inhibited IL-6-induced cell invasion and matrix metalloproteinase activation by blocking Raf/mitogen-activated protein kinase signaling activation[44].
Apoptosis induced by Res appears to be one of the inhibitory mechanisms involved in GC treatment. Res is a slow inducer of apoptosis; prolonged treatment with high concentrations of Res may result in apoptotic cell death and loss of cells[25,34]. The apoptosis may be attributed to the accumulation of peroxynitrite arising from the production of significant levels of NO[25]. Additionally, Res induces cell apoptosis via downregulating the expression of the apoptosis-inhibiting protein survivin[45], increasing generation of ROS[46], and downregulating senescence pathways such as cyclin D1, cyclin-dependent kinase 6 (CDK 6), CDK4, p16, and p21[47].
Apoptosis is usually mediated through two major pathways: The intrinsic pathway, induced by destabilization of mitochondria; and the extrinsic pathway, activated when extracellular ligands interact with receptors of the TNF family (TNF, FAS, and TRAIL). With mitochondria as the central gateway controllers and the B-cell lymphoma 2 (Bcl-2) family of proteins as executioners, the mitochondrial pathway is complex[48,49]. The Bcl-2 family plays an important role in the control of apoptosis, including anti-apoptotic proteins such as Bcl-2 and B-cell lymphoma-extra large (Bcl-xl), as well as pro-apoptotic proteins such as Bcl-2-associated X (Bax) and Bcl-2-associated agonist of cell death (Bad)[50,51]. Res was found to induce apoptosis by downregulating the anti-apoptotic gene Bcl-2 and upregulating the pro-apoptotic gene Bax[52,53]. It is also clear that activation of caspases is a hallmark of apoptosis promotion in response to death-inducing signals originating from mitochondria[53-55]. After treatment with Res, expression of the proapoptotic proteins cleaved caspase3 and cleaved caspase-8 are upregulated. Res also induces apoptosis by suppressing NF-κB activation[55]. Additionally, Res produces time- and concentration-dependent increases in the mitotic inhibitor p21(cip1/WAF-1) and the tumor suppressor p53[56]. The specific cell death signals engaged by Res appear to be cell type-dependent, particularly with respect to the p53 status of the cell[35,57]. Upregulation of both Fas and Fas-L proteins has been observed after Res treatment of p53-expressing SNU-1 cells, whereas in p53-deficient KATO-III cells, only Fas-L is increased[57]. Res and the sphingosine kinase inhibitor dimethylsphingosine (DMS) may be part of a common apoptotic signaling pathway. Res increases the cytotoxicity and p53 expression when combined with DMS[58].
Chemotherapy is considered to be the most effective treatment for patients with inoperable cancer; it provides palliative treatment of symptoms and improves patient QoL and survival[59]. However, conventional chemotherapeutic drugs such as doxorubicin (DOX) and platinum have been criticized due to their negative effects, including the development of drug resistance and the occurrence of tumors[60,61]. Xu et al[62] found that Res could reverse DOX resistance by reversing the EMT process via modulation of the PTEN/Akt signaling pathway.
Res may reduce the drug resistance of cancer cells by affecting the expression of several genes and proteins associated with multidrug resistance (MDR), including ATP binding cassette subfamily B member 1, annexin A1, and thioredoxin genes, as well as the proteins encoded by these genes[63]. Res can also reduce the expression levels of the aforementioned genes in the human GC cell line EPG85-257RDB and human GC cell line EPG85-257RNOV, which are resistant to daunorubicin and mitoxantrone, respectively[63].
Many studies have demonstrated that Res has promising preventive and therapeutic effects on CRC in vitro and in vivo. Cyclooxygenase-2 (COX-2) enzyme expression is usually upregulated during inflammation in most human adenocarcinomas and colonic tumors[64-66]. Res decreases COX-2 protein expression in CRC cells[67]. Chronic colitis is associated with CRC risk, and Res mixed with food ameliorates a dextran sulfate sodium mouse model of colitis[68]. Sirtuin 1 (SIRT-1) may induce inflammatory cytokines through the activation of NF-κB. Hofseth et al[69] found that Res can also reverse the downregulation of SIRT-1 during colitis.
Lipopolysaccharide (LPS), a principal component of the outer membrane of Gram-negative bacteria, plays a critical role in triggering an early inflammatory response. Res reduces the LPS-induced inflammatory response by interfering with LPS-induced NF-κB activation[70]. Nrf2 is recognized as a drug target for the prevention of CRC[71]. Res supplementation suppresses tumorigenesis in colitis-associated tumorigenesis mice. Downregulation of Nrf2 and its target genes have been observed in adenomas from adjacent normal tissue[72].
CRC is a pathological consequence of persistent oxidative stress, resulting in mutations and DNA damage in cancer-associated genes in which the cellular overproduction of ROS is implicated[73,74]. Sengottuvelan et al[74] demonstrated that 1,2-dimethylhydrazine (DMH)-induced DNA damage and oxidative stress were effectively suppressed by chronic Res supplementation. Particularly, entire-period Res supplementation increases enzymatic (glutathione reductase, superoxide dismutase, glutathione peroxidase, catalase and glutathione S-transferase) and non-enzymatic (reduced glutathione, vitamin C, vitamin E and β-carotene) anti-oxidant status with a corresponding decrease in the extent of lipid peroxidation markers such as thiobarbituric acid reactive substances, diene conjugates, and lipid hydroperoxides.
Res also exerts anti-proliferative activity in CRC similar to GC. There are several mechanisms involved in the anti-proliferative effects of Res. First, Res may inhibit the expression of ornithine decarboxylase, a key enzyme of polyamine biosynthesis that is enhanced in cancer growth[75]. Second, Res inhibits cell proliferation through modulating cyclin and CDK activities such as telomerase activity[76,77]. Relatively high concentrations (higher than 2.5 μg/mL) of Res have been found to downregulate telomerase activity[78]. Third, obesity is associated with elevated insulin-like growth factor-1 (IGF-1), which is related to various types of cancer including CRC[79]. Res inhibits IGF-1R protein levels, and the downstream Akt/Wnt signaling pathway, which plays a critical role in cell proliferation, is attenuated[80]. Finally, Liu et al[81] found that the anti-proliferative effects of Res may be mediated by regulation of the PTEN/PI3K/Akt and Wnt/β-catenin signaling separately. The exogenous expression of PTEN suppresses PI3K/Akt signaling and promotes the anti-proliferative effects of Res. The protein and mRNA expression of β-catenin is also decreased in a concentration-dependent manner[81].
Similar to GC, Res induces cell apoptosis in CRC through both intrinsic and extrinsic pathways[82]. In the intrinsic or mitochondrial pathway, Res can induce Bax-mediated and Bax-independent mitochondrial apoptosis. Res induces the co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis[83]. Res can also induce an early increase in mitochondrial ROS production upstream of caspase activation[84].
In the extrinsic pathway, Res induces redistribution of the Fas receptor in membrane rafts to trigger apoptosis[85]. Res also induces clustering and redistribution of Fas, which is associated with formation of a death-inducing signaling complex in cholesterol and sphingolipid-rich fractions of SW480 cells, together with Fas-associating protein with death domain and procaspase-8[85]. Apoptosis can also be initiated by lysosomes and the endoplasmic reticulum[86].
In addition, the mechanism by which Res induces apoptosis involves ROS-triggered autophagy. Inhibition of Res-induced autophagy causes significant attenuation in apoptosis accompanied by the decreased cleavage of casapse-8 and caspase-3[87]. Res-induced apoptosis can be partially mediated through the PKC-ERK1/2 signaling pathway[88-90]. Res significantly upregulates phosphorylation of PKCα and ERK1/2. Pre-treatment with PKCα and ERK1/2 inhibitors (Gő6976 and PD98059, respectively) promotes apoptosis[90].
Similar to GC, Res leads to the downregulation of MALAT1, consequently the invasion and metastasis of CRC can be inhibited. MALAT1 is also correlated with the Wnt/β-catenin signaling pathway, which regulates tumor cell invasion and metastasis[91]. Treatment with Res can also decrease the nuclear localization of β-catenin, resulting in attenuation of Wnt/β-catenin signaling. Morin et al[92] and Jeong et al[93] reported that transcription factor 4 (TCF4) is a molecular target of Res in the prevention of CRC. Res treatment downregulated the expression of TCF4 through ERK- and p38-dependent pathways[93]. In addition, decreased expression of tristetraprolin (TTP) is observed in patients with CRC[94]. Res suppresses the proliferation and invasion/metastasis by activating TTP[94]. It can reverse the proliferation and invasion induced by TNF-β, which is linked to suppression of the TNF-β-stimulated NF-κB signaling pathway[95-99]. In addition, Res suppresses TNF-β-promoted NF-κB-mediated gene biomarkers associated with proliferation, apoptosis, and invasion[95], induces morphological changes associated with the expression of EMT parameters (elevated vimentin and slug, reduced E-cadherin), and increases migration/invasion[100].
Vascular endothelial growth factor (VEGF) is an important angiogenic factor secreted by tumor cells, which stimulates tumor neo-angiogenesis and vascular permeability[101]. Res may decrease the level of VEGF in many cancer cells such as human leukemia (U937) cells, ovarian carcinoma cells, and breast cancer cells (MDAMB-231)[102-104]. Fouad et al[105] reported that Res can inhibit angiogenesis. VEGF protein secretion was significantly reduced in both Caco2 and HCT116 cells.
MDR is a common phenomenon in the clinic that requires immediate resolution. Several findings have indicated that Res chemosensitizes the anti-tumor effects of fluorouracil (5-FU) by inhibiting the EMT phenotype via the upregulation of intercellular junctions and downregulation of the NF-κB pathway[99]. Genotoxicity and apoptosis are increased when 5-FU-resistant cells are treated with Res and 1,3-Bis (2-chloroethyl)-1-nitrosourea[106]. In addition, this combined treatment decreases the levels of DNA polymerase beta, flap endonuclease 1, and DNA damage-binding protein 2, which are overexpressed in 5-FU-resistant cell lines[106]. Res also synergizes the invasion inhibitory effects of 5-FU. Res significantly attenuates drug resistance via suppression of EMT factors (decreased vimentin and slug, increased E-cadherin), diminished NF-κB activation and its translocation to the nucleus, and abolished NF-κB-regulated gene end products (matrix metalloproteinase 9, caspase-3)[107]. Further, Res can chemosensitize TNF-β-induced increased capacity for survival and invasion of HCT116R cells in response to 5-FU[108].
Moreover, Res can downregulate the expression of MDR1 to ameliorate cisplatin resistance[106,109]. Wang et al[110] also found that Res inhibits MDR1 expression in oxaliplatin (L-OHP)-resistant CRC cells HCT116 cells through inhibition of the NF-κB signaling pathway and activation of cAMP-response element binding protein in an 5' AMP-activated protein kinase-dependent manner. Table 1 summarizes the effect and targets/mechanisms of Res in GC and CRC.
Effect | Cell or animal model | Proposed targets/mechanisms | Ref. | |
Gastric cancer | Anti-H. pylori | MKN-45 cells | Inhibition of IL-8 secretion, inhibition of ROS generation | [27] |
Mice | Downregulation of IL-8 and iNOS, inhibition of NF-κB activity, activation of the Nrf2/HO-1 pathway | [30] | ||
Anti-proliferation | KATO-III cells | Inhibition of PKC activity | [34] | |
ACS cells | The MEK1/2-ERK1/2- c-Jun signaling pathway | [37] | ||
SNU-1 cells | The PTEN/ PI3K/Akt signaling pathway | [25] | ||
MGC803 cells | The PI3K/Akt signaling pathway | [38] | ||
MGC-803 cells | Downregulation of β-catenin, c-myc, and cyclin D1, inhibition of the Wnt/β-catenin pathway | [39] | ||
Inhibition of invasion and metastasis | SGC7901 cells | Inhibition of the Hh signaling pathway and EMT | [41] | |
SGC7901 cells | Inhibition of the Raf/MAPK signaling pathway | [44] | ||
BGC823 cells | Inhibition of MALAT1 | [42] | ||
Induction of apoptosis and senescence | SGC7901 cells | Downregulation of survivin | [45] | |
SGC-7901 cells | Increase of ROS | [46] | ||
AGS, BGC-823 and SGC-7901 cells | Downregulation of the senescence pathways such as cyclin D1, CDK 6 and CDK4, p16 and p21 | [47] | ||
Nude mice | Downregulation of anti-apoptotic gene bcl-2, up-regulation of the pro-apoptotic gene bax | [52] | ||
SGC 7901 cells | Upregulation of bax, cleaved caspase 3 and cleaved caspase 8, downregulation of bcl-2, inhibition of NF-κB activity | [53] | ||
SGC-7901 cells | Activation of caspase-3 and pro-caspase 9 was downregulated, the expression ratio of bax/bcl-2 was increased | [54] | ||
SNU-1 cells and KATO-III cells | Upregulation of both Fas and Fas-Lin SNU-1 cells, upregulation of Fas-L in KATO-III cells | [56] | ||
SNU-1, KATO- and RF-1 cells | SNU-1 cells: Upregulation of p53, downregulation of surviving; AGS cells: Upregulation of p53, stimulation of caspase 3 and cytochrome C oxidase activities; KATO-III cells (not expressing p53): Stimulation of caspase 3 and cytochrome C oxidase activities | [57] | ||
SNU-1 cells | Upregulation of p53 expression | [58] | ||
MDR | SGC7901/DOX | PTEN/Akt signaling pathway | [62] | |
RDB and RNOV | In RDB cells, Res reduced the expression level of all analyzed genes, so were results at the protein level obtained for P-gp and TXN. In turn, in the RNOV cell line, Res reduced TXN expression at mRNA and protein levels | [63] | ||
Colorectal cancer | Anti-inflammatory | HCA-7 cancer cells | Downregulation of COX-2 III | [67] |
Dextran Sulfate Sodium (DSS) mouse model of colitis | Decrease of CD3+ T cells, downregulation of p53 | [68] | ||
Caco-2 and SW480 cells | Inhibition of iNOS, decrease of NO production, inhibition of NF-κB activity | [70] | ||
Mice | Downregulation of Nrf2 | [72] | ||
Inhibit oxidative stress | Wistar male rats | Increase of the enzymic and non-enzymic antioxidant status | [74] | |
Anti-proliferation | CaCo-2 cells | Inhibition of ODC expression | [75] | |
SW480 cells | Modulation of cyclin and CDK activities | [76] | ||
HT-29 and WiDr cells | Downregulation of telomerase activity | [78] | ||
HT-29 cells | Inhibition of IGF-1R and the downstream Akt/Wnt signaling pathway | [80] | ||
HCT116 cells | Downregulation the PTEN/PI3K/Akt and Wnt/β-catenin signaling | [81] | ||
Induce apoptosis | HCT116 cells | Induction of bax, activation of caspases 3 and 9 | [83] | |
HT-29 cells | Production of O2-•, increase of mitochondrial ROS production | [84] | ||
SW480 cells | Redistribution of Fas | [85] | ||
HT-29 cells | Lysosomal cathepsin D demonstrated upstream of cytosolic caspase activation | [86] | ||
HT-29 cells | ROS-triggered autophagy, decrease of cleavage of casapse-8 and caspase-3 | [87] | ||
HT- 29 cells | The PKC- ERK1/2 signaling pathway | [90] | ||
Inhibit invasion and metastasis | LoVo and HCT116 cells | Downregulation of MALAT1, decrease of β-catenin attenuation of Wnt/β-catenin signaling | [91] | |
HCT116 cells | ERK and p38-dependent pathways, downregulation of TCF4 | [93] | ||
HCT116 and SNU81 colon cancer cells | Increase of TTP expression | [94] | ||
HCT116 cells | Suppression of NF-κB signaling pathway | [98] | ||
HCT116, RKO and SW480 cells | Decrease of TNF-β/TNF-βR-induced EMT, suppression of NF-βB and FAK | [99] | ||
Inhibition of angiogenesis | Caco2 cell and HCT116 cells | Reduction of VEGF level | [105] | |
Reversion of MDR | 5-FU-sensitive HCT-116 cells | Decrease of the levels of POL-β, POLH, FEN1and DDB2 | [106] | |
5-FU chemoresistance-derived clones HCT116R cells | Upregulation of intercellular junctions and downregulation of NF-κB pathway | [107] | ||
HCT116R cells | Suppression of tumor-promoting factors (NF-κB, MMP-9, CXCR4) activity and EMT factors | [108] | ||
CIS-resistant HCT 116 cells | Increase in the early apoptosis fraction and enhance the subsequent apoptotic effects of CIS | [109] | ||
HCT116/LOHP | Downregulation of mRNA and P-gp/MDR1 and MDR1 promoter activity | [110] |
Despite all of the documented potential anti-cancer effects of Res in cell culture models and animal models, we cannot assume that the potential properties of Res can be translated to humans because of the low bioavailability of Res. Due to the rapid metabolism and glucuronidation and sulfation in the intestine and liver, the bioavailability of Res in humans is considerably less than 1%[111,112] despite high absorption of almost 70%[113,114]. The poor bioavailability of Res is an important problem in terms of extrapolating its potential clinical application. Several methods have been developed to improve its bioavailability, such as utilizing it in combination with an additional phytochemical curcumin or using nanotechnological formulations[115,116].
Xu et al[117] reported that combined treatment with curcumin and Res in DMH-treated GC rats led to regulation of both p53 phosphorylation and acetylation, which activated stable tumor suppressor p53 against GC. Gavrilas et al[118] also investigated cell proliferation inhibitory effect of the combined treatment of curcumin and Res, and found synergistic effects in both DLD-1 and Caco-2 cells. The expression of several apoptosis regulatory genes including PMAIP1, BID, ZMAT3, and FAS was significantly increased, representing novel targets of combined treatment with curcumin and Res[117,118].
Lipid-core nanocapsules (LNCs) also reportedly stabilize the incorporated drugs, control their release pattern, and increase the activity of the drugs in the body[119]. Feng et al[120] prepared Res-loaded LNCs (RSV-LNCs) and found that they exerted a remarkable reduction in cell apoptosis of approximately 36%. This suggests that RSV-LNCs have superior anti-cancer effects and promising potential to increase the therapeutic efficacy of Res[120].
GI cancer, particularly CG and CRC, is a highly prevalent cancer and one of the leading causes of cancer-related deaths worldwide. Multiple molecular mechanisms, including inflammation, oxidative stress, cell proliferation, and apoptosis, are associated with its incidence and progression[121,122]. Res is a polyphenol compound with a variety of properties including anti-inflammatory, cell proliferation inhibition, and apoptosis properties[123,124]. Multiple studies have demonstrated the potential effects of Res for the treatment of GC and CRC. This phytochemical has multiple advantages, is comparatively safe, and is able to target multiple cell signaling pathways. However, the bioavailability of Res is very low in humans and a high dose may not reach a sufficient concentration of treatment due to the metabolic characteristics[125]. Res may be of benefit for digestive tract cancer treatment as it is efficiently absorbed in the GI tract and exerts local effects before its metabolization[126,127]. Although various methods have been developed to improve the bioavailability of Res, more studies are needed to verify the efficacy of Res in GI cancer.
Manuscript source: Invited manuscript
Specialty type: Medicine, Research and Experimental
Country/Territory of origin: China
Peer-review report’s scientific quality classification
Grade A (Excellent): 0
Grade B (Very good): 0
Grade C (Good): C
Grade D (Fair): D
Grade E (Poor): 0
P-Reviewer: Bourgoin SG, Hori T S-Editor: Dou Y L-Editor: Filipodia E-Editor: Liu JH
1. | Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 53206] [Cited by in F6Publishing: 52883] [Article Influence: 8813.8] [Reference Citation Analysis (123)] |
2. | Raskov H, Pommergaard HC, Burcharth J, Rosenberg J. Colorectal carcinogenesis--update and perspectives. World J Gastroenterol. 2014;20:18151-18164. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 106] [Cited by in F6Publishing: 116] [Article Influence: 11.6] [Reference Citation Analysis (0)] |
3. | Wu K, Nie Y, Guo C, Chen Y, Ding J, Fan D. Molecular basis of therapeutic approaches to gastric cancer. J Gastroenterol Hepatol. 2009;24:37-41. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 49] [Cited by in F6Publishing: 57] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
4. | Sabit H, Cevik E, Tombuloglu H. Colorectal cancer: The epigenetic role of microbiome. World J Clin Cases. 2019;7:3683-3697. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 22] [Cited by in F6Publishing: 17] [Article Influence: 3.4] [Reference Citation Analysis (4)] |
5. | Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011;55:1129-1141. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 408] [Cited by in F6Publishing: 385] [Article Influence: 29.6] [Reference Citation Analysis (0)] |
6. | Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337-342. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3166] [Cited by in F6Publishing: 3162] [Article Influence: 175.7] [Reference Citation Analysis (0)] |
7. | Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493-506. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2705] [Cited by in F6Publishing: 2701] [Article Influence: 150.1] [Reference Citation Analysis (0)] |
8. | Frémont L. Biological effects of resveratrol. Life Sci. 2000;66:663-673. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1160] [Cited by in F6Publishing: 1078] [Article Influence: 44.9] [Reference Citation Analysis (0)] |
9. | Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218-220. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3633] [Cited by in F6Publishing: 3344] [Article Influence: 123.9] [Reference Citation Analysis (0)] |
10. | Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French paradox revisited. Front Pharmacol. 2012;3:141. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 270] [Cited by in F6Publishing: 286] [Article Influence: 23.8] [Reference Citation Analysis (0)] |
11. | Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284:1328-1333. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 795] [Cited by in F6Publishing: 755] [Article Influence: 30.2] [Reference Citation Analysis (0)] |
12. | Keates S, Hitti YS, Upton M, Kelly CP. Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology. 1997;113:1099-1109. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 322] [Cited by in F6Publishing: 334] [Article Influence: 12.4] [Reference Citation Analysis (0)] |
13. | Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol. 2019;25:4870-4884. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 72] [Cited by in F6Publishing: 69] [Article Influence: 13.8] [Reference Citation Analysis (2)] |
14. | Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:177-240. [PubMed] [Cited in This Article: ] |
15. | Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 2015;136:487-490. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 643] [Cited by in F6Publishing: 616] [Article Influence: 68.4] [Reference Citation Analysis (0)] |
16. | Bodger K, Crabtree JE. Helicobacter pylori and gastric inflammation. Br Med Bull. 1998;54:139-150. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 123] [Cited by in F6Publishing: 131] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
17. | Chen MY, He CY, Meng X, Yuan Y. Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer. World J Gastroenterol. 2013;19:4242-4251. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 40] [Cited by in F6Publishing: 38] [Article Influence: 3.5] [Reference Citation Analysis (1)] |
18. | Li H, Xu CX, Gong RJ, Chi JS, Liu P, Liu XM. How does Helicobacter pylori cause gastric cancer through connexins: An opinion review. World J Gastroenterol. 2019;25:5220-5232. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 7] [Cited by in F6Publishing: 7] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
19. | Liu XM, Xu CX, Zhang LF, Huang LH, Hu TZ, Li R, Xia XJ, Xu LY, Luo L, Jiang XX, Li M. PBX1 attributes as a determinant of connexin 32 downregulation in Helicobacter pylori-related gastric carcinogenesis. World J Gastroenterol. 2017;23:5345-5355. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 7] [Cited by in F6Publishing: 7] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
20. | Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol. 2017;23:1521-1540. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 79] [Cited by in F6Publishing: 78] [Article Influence: 11.1] [Reference Citation Analysis (1)] |
21. | Lee KW, Bode AM, Dong Z. Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer. 2011;11:211-218. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 316] [Cited by in F6Publishing: 288] [Article Influence: 22.2] [Reference Citation Analysis (0)] |
22. | Chung JY, Park JO, Phyu H, Dong Z, Yang CS. Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7b Ras 12 cells by tea polyphenols (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate. FASEB J. 2001;15:2022-2024. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 126] [Cited by in F6Publishing: 132] [Article Influence: 5.7] [Reference Citation Analysis (0)] |
23. | Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003;63:7563-7570. [PubMed] [Cited in This Article: ] |
24. | Ye F, Zhang GH, Guan BX, Xu XC. Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin. World J Gastroenterol. 2012;18:126-135. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 60] [Cited by in F6Publishing: 56] [Article Influence: 4.7] [Reference Citation Analysis (0)] |
25. | Holian O, Wahid S, Atten MJ, Attar BM. Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide. Am J Physiol Gastrointest Liver Physiol. 2002;282:G809-G816. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 57] [Cited by in F6Publishing: 54] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
26. | Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Immun. 2007;75:4030-4039. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 137] [Cited by in F6Publishing: 140] [Article Influence: 8.2] [Reference Citation Analysis (0)] |
27. | Zaidi SF, Ahmed K, Yamamoto T, Kondo T, Usmanghani K, Kadowaki M, Sugiyama T. Effect of resveratrol on Helicobacter pylori-induced interleukin-8 secretion, reactive oxygen species generation and morphological changes in human gastric epithelial cells. Biol Pharm Bull. 2009;32:1931-1935. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 41] [Cited by in F6Publishing: 46] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
28. | Rieder G, Hofmann JA, Hatz RA, Stolte M, Enders GA. Up-regulation of inducible nitric oxide synthase in Helicobacter pylori-associated gastritis may represent an increased risk factor to develop gastric carcinoma of the intestinal type. Int J Med Microbiol. 2003;293:403-412. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 45] [Cited by in F6Publishing: 48] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
29. | Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749-759. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2227] [Cited by in F6Publishing: 2328] [Article Influence: 122.5] [Reference Citation Analysis (0)] |
30. | Zhang X, Jiang A, Qi B, Ma Z, Xiong Y, Dou J, Wang J. Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress. Int J Mol Sci. 2015;16:27757-27769. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 41] [Cited by in F6Publishing: 49] [Article Influence: 5.4] [Reference Citation Analysis (0)] |
31. | Watson AJ. An overview of apoptosis and the prevention of colorectal cancer. Crit Rev Oncol Hematol. 2006;57:107-121. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 76] [Cited by in F6Publishing: 73] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
32. | Gautam SC, Xu YX, Dumaguin M, Janakiraman N, Chapman RA. Resveratrol selectively inhibits leukemia cells: a prospective agent for ex vivo bone marrow purging. Bone Marrow Transplant. 2000;25:639-645. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 80] [Cited by in F6Publishing: 83] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
33. | Godichaud S, Krisa S, Couronné B, Dubuisson L, Mérillon JM, Desmoulière A, Rosenbaum J. Deactivation of cultured human liver myofibroblasts by trans-resveratrol, a grapevine-derived polyphenol. Hepatology. 2000;31:922-931. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 86] [Cited by in F6Publishing: 87] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
34. | Atten MJ, Attar BM, Milson T, Holian O. Resveratrol-induced inactivation of human gastric adenocarcinoma cells through a protein kinase C-mediated mechanism. Biochem Pharmacol. 2001;62:1423-1432. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 59] [Cited by in F6Publishing: 62] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
35. | Atten MJ, Godoy-Romero E, Attar BM, Milson T, Zopel M, Holian O. Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells. Invest New Drugs. 2005;23:111-119. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 71] [Cited by in F6Publishing: 71] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
36. | Lavin MF, Watters D, Song Q. Role of protein kinase activity in apoptosis. Experientia. 1996;52:979-994. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 51] [Cited by in F6Publishing: 55] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
37. | Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. trans-Resveratrol inhibits H2O2-induced adenocarcinoma gastric cells proliferation via inactivation of MEK1/2-ERK1/2-c-Jun signalling axis. Biochem Pharmacol. 2009;77:337-347. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 24] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
38. | Dai H, Deng HB, Wang YH, Guo JJ. Resveratrol inhibits the growth of gastric cancer via the Wnt/β-catenin pathway. Oncol Lett. 2018;16:1579-1583. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 10] [Cited by in F6Publishing: 17] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
39. | Jing X, Cheng W, Wang S, Li P, He L. Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway. Oncol Rep. 2016;35:472-478. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 45] [Cited by in F6Publishing: 53] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
40. | Busquets S, Ametller E, Fuster G, Olivan M, Raab V, Argilés JM, López-Soriano FJ. Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Lett. 2007;245:144-148. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 53] [Cited by in F6Publishing: 49] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
41. | Gao Q, Yuan Y, Gan HZ, Peng Q. Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis. Oncol Lett. 2015;9:2381-2387. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 56] [Cited by in F6Publishing: 64] [Article Influence: 7.1] [Reference Citation Analysis (0)] |
42. | Yang Z, Xie Q, Chen Z, Ni H, Xia L, Zhao Q, Chen Z, Chen P. Resveratrol suppresses the invasion and migration of human gastric cancer cells via inhibition of MALAT1-mediated epithelial-to-mesenchymal transition. Exp Ther Med. 2019;17:1569-1578. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 12] [Cited by in F6Publishing: 22] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
43. | Rokavec M, Öner MG, Li H, Jackstadt R, Jiang L, Lodygin D, Kaller M, Horst D, Ziegler PK, Schwitalla S, Slotta-Huspenina J, Bader FG, Greten FR, Hermeking H. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest. 2014;124:1853-1867. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 457] [Cited by in F6Publishing: 585] [Article Influence: 58.5] [Reference Citation Analysis (0)] |
44. | Yang T, Zhang J, Zhou J, Zhu M, Wang L, Yan L. Resveratrol inhibits Interleukin-6 induced invasion of human gastric cancer cells. Biomed Pharmacother. 2018;99:766-773. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 30] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
45. | Liu ML, Zhang SJ. Effects of resveratrol on the protein expression of survivin and cell apoptosis in human gastric cancer cells. J BUON. 2014;19:713-717. [PubMed] [Cited in This Article: ] |
46. | Wang Z, Li W, Meng X, Jia B. Resveratrol induces gastric cancer cell apoptosis via reactive oxygen species, but independent of sirtuin1. Clin Exp Pharmacol Physiol. 2012;39:227-232. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 43] [Cited by in F6Publishing: 40] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
47. | Yang Q, Wang B, Zang W, Wang X, Liu Z, Li W, Jia J. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One. 2013;8:e70627. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 96] [Cited by in F6Publishing: 97] [Article Influence: 8.8] [Reference Citation Analysis (0)] |
48. | Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309-1312. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 6842] [Cited by in F6Publishing: 6751] [Article Influence: 259.7] [Reference Citation Analysis (0)] |
49. | Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770-776. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5259] [Cited by in F6Publishing: 5147] [Article Influence: 214.5] [Reference Citation Analysis (0)] |
50. | Chen GG, Lai PB, Hu X, Lam IK, Chak EC, Chun YS, Lau WY. Negative correlation between the ratio of Bax to Bcl-2 and the size of tumor treated by culture supernatants from Kupffer cells. Clin Exp Metastasis. 2002;19:457-464. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 15] [Article Influence: 0.7] [Reference Citation Analysis (0)] |
51. | Pettersson F, Dalgleish AG, Bissonnette RP, Colston KW. Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax. Br J Cancer. 2002;87:555-561. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 92] [Cited by in F6Publishing: 99] [Article Influence: 4.5] [Reference Citation Analysis (0)] |
52. | Zhou HB, Chen JJ, Wang WX, Cai JT, Du Q. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice. World J Gastroenterol. 2005;11:280-284. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 70] [Cited by in F6Publishing: 66] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
53. | Yang Y, Huang X, Chen S, Ma G, Zhu M, Yan F, Yu J. Resveratrol induced apoptosis in human gastric carcinoma SGC-7901 cells via activation of mitochondrial pathway. Asia Pac J Clin Oncol. 2018;14:e317-e324. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 8] [Cited by in F6Publishing: 10] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
54. | Yang L, Wu S, Zhang Q, Liu F, Wu P. 23,24-Dihydrocucurbitacin B induces G2/M cell-cycle arrest and mitochondria-dependent apoptosis in human breast cancer cells (Bcap37). Cancer Lett. 2007;256:267-278. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 64] [Cited by in F6Publishing: 69] [Article Influence: 4.1] [Reference Citation Analysis (0)] |
55. | Wu X, Xu Y, Zhu B, Liu Q, Yao Q, Zhao G. Resveratrol induces apoptosis in SGC-7901 gastric cancer cells. Oncol Lett. 2018;16:2949-2956. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 12] [Cited by in F6Publishing: 19] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
56. | Livneh E, Fishman DD. Linking protein kinase C to cell-cycle control. Eur J Biochem. 1997;248:1-9. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 174] [Cited by in F6Publishing: 177] [Article Influence: 6.6] [Reference Citation Analysis (0)] |
57. | Riles WL, Erickson J, Nayyar S, Atten MJ, Attar BM, Holian O. Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells. World J Gastroenterol. 2006;12:5628-5634. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 28] [Cited by in F6Publishing: 25] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
58. | Shin KO, Park NY, Seo CH, Hong SP, Oh KW, Hong JT, Han SK, Lee YM. Inhibition of sphingolipid metabolism enhances resveratrol chemotherapy in human gastric cancer cells. Biomol Ther (Seoul). 2012;20:470-476. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 22] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
59. | Li B, Chen L, Luo HL, Yi FM, Wei YP, Zhang WX. Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin, cisplatin, and 5-fluorouracil regimen for advanced gastric cancer: A systematic review and meta-analysis. World J Clin Cases. 2019;7:600-615. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 8] [Cited by in F6Publishing: 9] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
60. | Xavier LL, Viola GG, Ferraz AC, Da Cunha C, Deonizio JM, Netto CA, Achaval M. A simple and fast densitometric method for the analysis of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area. Brain Res Brain Res Protoc. 2005;16:58-64. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 146] [Cited by in F6Publishing: 149] [Article Influence: 7.8] [Reference Citation Analysis (0)] |
61. | Broxterman HJ, Gotink KJ, Verheul HM. Understanding the causes of multidrug resistance in cancer: a comparison of doxorubicin and sunitinib. Drug Resist Updat. 2009;12:114-126. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 154] [Cited by in F6Publishing: 158] [Article Influence: 10.5] [Reference Citation Analysis (0)] |
62. | Xu J, Liu D, Niu H, Zhu G, Xu Y, Ye D, Li J, Zhang Q. Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. J Exp Clin Cancer Res. 2017;36:19. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 138] [Cited by in F6Publishing: 184] [Article Influence: 26.3] [Reference Citation Analysis (0)] |
63. | Mieszala K, Rudewicz M, Gomulkiewicz A, Ratajczak-Wielgomas K, Grzegrzolka J, Dziegiel P, Borska S. Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol. Oncol Lett. 2018;15:5825-5832. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 8] [Cited by in F6Publishing: 10] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
64. | Hansen-Petrik MB, McEntee MF, Jull B, Shi H, Zemel MB, Whelan J. Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min/+) mice. Cancer Res. 2002;62:403-408. [PubMed] [Cited in This Article: ] |
65. | Uefuji K, Ichikura T, Mochizuki H. Expression of cyclooxygenase-2 in human gastric adenomas and adenocarcinomas. J Surg Oncol. 2001;76:26-30. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 9] [Reference Citation Analysis (0)] |
66. | Hull MA, Booth JK, Tisbury A, Scott N, Bonifer C, Markham AF, Coletta PL. Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice. Br J Cancer. 1999;79:1399-1405. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 94] [Cited by in F6Publishing: 97] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
67. | Sale S, Tunstall RG, Ruparelia KC, Potter GA, Steward WP, Gescher AJ. Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'-tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human-derived colon cancer cells. Int J Cancer. 2005;115:194-201. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 133] [Cited by in F6Publishing: 135] [Article Influence: 7.1] [Reference Citation Analysis (0)] |
68. | Cui X, Jin Y, Hofseth AB, Pena E, Habiger J, Chumanevich A, Poudyal D, Nagarkatti M, Nagarkatti PS, Singh UP, Hofseth LJ. Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prev Res (Phila). 2010;3:549-559. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 145] [Cited by in F6Publishing: 144] [Article Influence: 10.3] [Reference Citation Analysis (0)] |
69. | Hofseth LJ, Singh UP, Singh NP, Nagarkatti M, Nagarkatti PS. Taming the beast within: resveratrol suppresses colitis and prevents colon cancer. Aging (Albany NY). 2010;2:183-184. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 25] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
70. | Panaro MA, Carofiglio V, Acquafredda A, Cavallo P, Cianciulli A. Anti-inflammatory effects of resveratrol occur via inhibition of lipopolysaccharide-induced NF-κB activation in Caco-2 and SW480 human colon cancer cells. Br J Nutr. 2012;108:1623-1632. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 78] [Cited by in F6Publishing: 96] [Article Influence: 8.0] [Reference Citation Analysis (0)] |
71. | Li J, Wang H, Zheng Z, Luo L, Wang P, Liu K, Namani A, Jiang Z, Wang XJ, Tang X. Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation. Free Radic Biol Med. 2018;124:541-549. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 42] [Cited by in F6Publishing: 42] [Article Influence: 7.0] [Reference Citation Analysis (0)] |
72. | Zheng Z, Chen Y, Huang J, Deng H, Tang X, Wang XJ. Mkp-1 is required for chemopreventive activity of butylated hydroxyanisole and resveratrol against colitis-associated colon tumorigenesis. Food Chem Toxicol. 2019;127:72-80. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 16] [Cited by in F6Publishing: 16] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
73. | Kinjo T, Suzui M, Morioka T, Nabandith V, Inamine M, Kaneshiro T, Arakaki J, Nishimaki T, Yoshimi N. Distribution of preneoplastic lesions and tumors, and beta-catenin gene mutations in colon carcinomas induced by 1,2-dimethylhydrazine plus dextran sulfate sodium. J Exp Clin Cancer Res. 2006;25:89-95. [PubMed] [Cited in This Article: ] |
74. | Sengottuvelan M, Deeptha K, Nalini N. Resveratrol ameliorates DNA damage, prooxidant and antioxidant imbalance in 1,2-dimethylhydrazine induced rat colon carcinogenesis. Chem Biol Interact. 2009;181:193-201. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 47] [Cited by in F6Publishing: 42] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
75. | Schneider Y, Vincent F, Duranton B, Badolo L, Gossé F, Bergmann C, Seiler N, Raul F. Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000;158:85-91. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 253] [Cited by in F6Publishing: 255] [Article Influence: 10.6] [Reference Citation Analysis (0)] |
76. | Delmas D, Passilly-Degrace P, Jannin B, Cherkaoui Malki M, Latruffe N. Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells. Int J Mol Med. 2002;10:193-199. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 9] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
77. | Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011-2015. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5156] [Cited by in F6Publishing: 5153] [Article Influence: 171.8] [Reference Citation Analysis (0)] |
78. | Fuggetta MP, Lanzilli G, Tricarico M, Cottarelli A, Falchetti R, Ravagnan G, Bonmassar E. Effect of resveratrol on proliferation and telomerase activity of human colon cancer cells in vitro. J Exp Clin Cancer Res. 2006;25:189-193. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 19] [Article Influence: 1.1] [Reference Citation Analysis (0)] |
79. | LeRoith D, Roberts CT Jr. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195:127-137. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 778] [Cited by in F6Publishing: 780] [Article Influence: 37.1] [Reference Citation Analysis (0)] |
80. | Vanamala J, Reddivari L, Radhakrishnan S, Tarver C. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer. 2010;10:238. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 174] [Cited by in F6Publishing: 169] [Article Influence: 12.1] [Reference Citation Analysis (0)] |
81. | Liu YZ, Wu K, Huang J, Liu Y, Wang X, Meng ZJ, Yuan SX, Wang DX, Luo JY, Zuo GW, Yin LJ, Chen L, Deng ZL, Yang JQ, Sun WJ, He BC. The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int J Oncol. 2014;45:104-112. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 79] [Article Influence: 7.9] [Reference Citation Analysis (0)] |
82. | Kanczuga-Koda L, Sulkowski S, Koda M, Skrzydlewska E, Sulkowska M. Connexin 26 correlates with Bcl-xL and Bax proteins expression in colorectal cancer. World J Gastroenterol. 2005;11:1544-1548. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 27] [Cited by in F6Publishing: 28] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
83. | Mahyar-Roemer M, Köhler H, Roemer K. Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells. BMC Cancer. 2002;2:27. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 57] [Cited by in F6Publishing: 58] [Article Influence: 2.6] [Reference Citation Analysis (0)] |
84. | Juan ME, Wenzel U, Daniel H, Planas JM. Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem. 2008;56:4813-4818. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 150] [Cited by in F6Publishing: 140] [Article Influence: 8.8] [Reference Citation Analysis (0)] |
85. | Delmas D, Rébé C, Lacour S, Filomenko R, Athias A, Gambert P, Cherkaoui-Malki M, Jannin B, Dubrez-Daloz L, Latruffe N, Solary E. Resveratrol-induced apoptosis is associated with Fas redistribution in the rafts and the formation of a death-inducing signaling complex in colon cancer cells. J Biol Chem. 2003;278:41482-41490. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 208] [Cited by in F6Publishing: 211] [Article Influence: 10.0] [Reference Citation Analysis (0)] |
86. | Trincheri NF, Nicotra G, Follo C, Castino R, Isidoro C. Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis. 2007;28:922-931. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 87] [Cited by in F6Publishing: 96] [Article Influence: 5.3] [Reference Citation Analysis (0)] |
87. | Miki H, Uehara N, Kimura A, Sasaki T, Yuri T, Yoshizawa K, Tsubura A. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol. 2012;40:1020-1028. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 142] [Cited by in F6Publishing: 152] [Article Influence: 12.7] [Reference Citation Analysis (0)] |
88. | Kim MJ, Park IJ, Yun H, Kang I, Choe W, Kim SS, Ha J. AMP-activated protein kinase antagonizes pro-apoptotic extracellular signal-regulated kinase activation by inducing dual-specificity protein phosphatases in response to glucose deprivation in HCT116 carcinoma. J Biol Chem. 2010;285:14617-14627. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 38] [Cited by in F6Publishing: 40] [Article Influence: 2.9] [Reference Citation Analysis (0)] |
89. | Davies CC, Chakraborty A, Cipriani F, Haigh K, Haigh JJ, Behrens A. Identification of a co-activator that links growth factor signalling to c-Jun/AP-1 activation. Nat Cell Biol. 2010;12:963-972. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 29] [Cited by in F6Publishing: 35] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
90. | Fang JY, Li ZH, Li Q, Huang WS, Kang L, Wang JP. Resveratrol affects protein kinase C activity and promotes apoptosis in human colon carcinoma cells. Asian Pac J Cancer Prev. 2012;13:6017-6022. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 15] [Article Influence: 1.9] [Reference Citation Analysis (0)] |
91. | Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J, Li Q. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS One. 2013;8:e78700. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 240] [Cited by in F6Publishing: 289] [Article Influence: 26.3] [Reference Citation Analysis (0)] |
92. | Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787-1790. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2986] [Cited by in F6Publishing: 3053] [Article Influence: 113.1] [Reference Citation Analysis (0)] |
93. | Jeong JB, Lee J, Lee SH. TCF4 Is a Molecular Target of Resveratrol in the Prevention of Colorectal Cancer. Int J Mol Sci. 2015;16:10411-10425. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 22] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
94. | Lee SR, Jin H, Kim WT, Kim WJ, Kim SZ, Leem SH, Kim SM. Tristetraprolin activation by resveratrol inhibits the proliferation and metastasis of colorectal cancer cells. Int J Oncol. 2018;53:1269-1278. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 15] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
95. | Deng K, Wang H, Shan T, Chen Y, Zhou H, Zhao Q, Xia J. Tristetraprolin inhibits gastric cancer progression through suppression of IL-33. Sci Rep. 2016;6:24505. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 28] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
96. | Pandiri I, Chen Y, Joe Y, Kim HJ, Park J, Chung HT, Park JW. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells. Breast Cancer Res Treat. 2016;156:57-64. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 8] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
97. | Wei ZR, Liang C, Feng D, Cheng YJ, Wang WM, Yang DJ, Wang YX, Cai QP. Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer. Oncotarget. 2016;7:17737-17750. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 17] [Cited by in F6Publishing: 20] [Article Influence: 2.9] [Reference Citation Analysis (0)] |
98. | Buhrmann C, Yazdi M, Popper B, Shayan P, Goel A, Aggarwal BB, Shakibaei M. Evidence that TNF-β induces proliferation in colorectal cancer cells and resveratrol can down-modulate it. Exp Biol Med (Maywood). 2019;244:1-12. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 33] [Article Influence: 6.6] [Reference Citation Analysis (0)] |
99. | Buhrmann C, Yazdi M, Popper B, Kunnumakkara AB, Aggarwal BB, Shakibaei M. Induction of the Epithelial-to-Mesenchymal Transition of Human Colorectal Cancer by Human TNF-β (Lymphotoxin) and its Reversal by Resveratrol. Nutrients. 2019;11. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 37] [Cited by in F6Publishing: 50] [Article Influence: 10.0] [Reference Citation Analysis (0)] |
100. | Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9:265-273. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2456] [Cited by in F6Publishing: 2525] [Article Influence: 168.3] [Reference Citation Analysis (0)] |
101. | Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932-936. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2451] [Cited by in F6Publishing: 2458] [Article Influence: 136.6] [Reference Citation Analysis (0)] |
102. | Tang Z, Liu XY, Zou P. Resveratrol inhibits the secretion of vascular endothelial growth factor and subsequent proliferation in human leukemia U937 cells. J Huazhong Univ Sci Technolog Med Sci. 2007;27:508-512. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 14] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
103. | Cao Z, Fang J, Xia C, Shi X, Jiang BH. trans-3,4,5'-Trihydroxystibene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells. Clin Cancer Res. 2004;10:5253-5263. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 123] [Cited by in F6Publishing: 131] [Article Influence: 6.9] [Reference Citation Analysis (0)] |
104. | Garvin S, Ollinger K, Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett. 2006;231:113-122. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 236] [Cited by in F6Publishing: 231] [Article Influence: 12.8] [Reference Citation Analysis (0)] |
105. | Fouad MA, Agha AM, Merzabani MM, Shouman SA. Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: calorie restriction is the force to the cytotoxicity. Hum Exp Toxicol. 2013;32:1067-1080. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 59] [Cited by in F6Publishing: 63] [Article Influence: 5.7] [Reference Citation Analysis (0)] |
106. | Das D, Preet R, Mohapatra P, Satapathy SR, Kundu CN. 1,3-Bis(2-chloroethyl)-1-nitrosourea enhances the inhibitory effect of resveratrol on 5-fluorouracil sensitive/resistant colon cancer cells. World J Gastroenterol. 2013;19:7374-7388. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 29] [Cited by in F6Publishing: 28] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
107. | Buhrmann C, Shayan P, Kraehe P, Popper B, Goel A, Shakibaei M. Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer. Biochem Pharmacol. 2015;98:51-68. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 92] [Cited by in F6Publishing: 107] [Article Influence: 11.9] [Reference Citation Analysis (0)] |
108. | Buhrmann C, Yazdi M, Popper B, Shayan P, Goel A, Aggarwal BB, Shakibaei M. Resveratrol Chemosensitizes TNF-β-Induced Survival of 5-FU-Treated Colorectal Cancer Cells. Nutrients. 2018;10. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 60] [Cited by in F6Publishing: 72] [Article Influence: 12.0] [Reference Citation Analysis (1)] |
109. | Osman AM, Al-Malki HS, Al-Harthi SE, El-Hanafy AA, Elashmaoui HM, Elshal MF. Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells. Mol Med Rep. 2015;12:1368-1374. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 15] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
110. | Wang Z, Zhang L, Ni Z, Sun J, Gao H, Cheng Z, Xu J, Yin P. Resveratrol induces AMPK-dependent MDR1 inhibition in colorectal cancer HCT116/L-OHP cells by preventing activation of NF-κB signaling and suppressing cAMP-responsive element transcriptional activity. Tumour Biol. 2015;36:9499-9510. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 43] [Cited by in F6Publishing: 35] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
111. | Wenzel E, Somoza V. Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res. 2005;49:472-481. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 465] [Cited by in F6Publishing: 476] [Article Influence: 25.1] [Reference Citation Analysis (0)] |
112. | Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fogliano V, Marchelli R. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005;49:495-504. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 218] [Cited by in F6Publishing: 211] [Article Influence: 11.1] [Reference Citation Analysis (0)] |
113. | de Santi C, Pietrabissa A, Mosca F, Pacifici GM. Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver. Xenobiotica. 2000;30:1047-1054. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 97] [Cited by in F6Publishing: 99] [Article Influence: 4.1] [Reference Citation Analysis (0)] |
114. | De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM. Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum. Xenobiotica. 2000;30:609-617. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 88] [Cited by in F6Publishing: 82] [Article Influence: 3.4] [Reference Citation Analysis (0)] |
115. | Liang L, Liu X, Wang Q, Cheng S, Zhang S, Zhang M. Pharmacokinetics, tissue distribution and excretion study of resveratrol and its prodrug 3,5,4'-tri-O-acetylresveratrol in rats. Phytomedicine. 2013;20:558-563. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 74] [Cited by in F6Publishing: 71] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
116. | Wang S, Su R, Nie S, Sun M, Zhang J, Wu D, Moustaid-Moussa N. Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. J Nutr Biochem. 2014;25:363-376. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 263] [Cited by in F6Publishing: 260] [Article Influence: 23.6] [Reference Citation Analysis (0)] |
117. | Xu H, Yu WB, Gao Y, Zhang MJ, Malhotra A, Yu WH. Modulatory Potential of Curcumin and Resveratrol on p53 Post-Translational Modifications during Gastric Cancer. J Environ Pathol Toxicol Oncol. 2018;37:93-101. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 7] [Cited by in F6Publishing: 8] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
118. | Gavrilas LI, Cruceriu D, Ionescu C, Miere D, Balacescu O. Pro-apoptotic genes as new targets for single and combinatorial treatments with resveratrol and curcumin in colorectal cancer. Food Funct. 2019;10:3717-3726. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 25] [Cited by in F6Publishing: 35] [Article Influence: 7.0] [Reference Citation Analysis (0)] |
119. | Külkamp IC, Rabelo BD, Berlitz SJ, Isoppo M, Bianchin MD, Schaffazick SR, Pohlmann AR, Guterres SS. Nanoencapsulation improves the in vitro antioxidant activity of lipoic acid. J Biomed Nanotechnol. 2011;7:598-607. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 32] [Cited by in F6Publishing: 34] [Article Influence: 2.6] [Reference Citation Analysis (0)] |
120. | Feng M, Zhong LX, Zhan ZY, Huang ZH, Xiong JP. Enhanced antitumor efficacy of resveratrol-loaded nanocapsules in colon cancer cells: physicochemical and biological characterization. Eur Rev Med Pharmacol Sci. 2017;21:375-382. [PubMed] [Cited in This Article: ] |
121. | Chung MY, Lim TG, Lee KW. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. World J Gastroenterol. 2013;19:984-993. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 52] [Cited by in F6Publishing: 41] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
122. | Yin TF, Wang M, Qing Y, Lin YM, Wu D. Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms. World J Gastroenterol. 2016;22:7058-7068. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 37] [Cited by in F6Publishing: 31] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
123. | Vacante M, Borzì AM, Basile F, Biondi A. Biomarkers in colorectal cancer: Current clinical utility and future perspectives. World J Clin Cases. 2018;6:869-881. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 81] [Cited by in F6Publishing: 96] [Article Influence: 16.0] [Reference Citation Analysis (2)] |
124. | Li YH, Niu YB, Sun Y, Zhang F, Liu CX, Fan L, Mei QB. Role of phytochemicals in colorectal cancer prevention. World J Gastroenterol. 2015;21:9262-9272. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 66] [Cited by in F6Publishing: 61] [Article Influence: 6.8] [Reference Citation Analysis (1)] |
125. | Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007;16:1246-1252. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 588] [Cited by in F6Publishing: 588] [Article Influence: 34.6] [Reference Citation Analysis (0)] |
126. | Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M. Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol. Carcinogenesis. 2002;23:1531-1536. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 120] [Cited by in F6Publishing: 125] [Article Influence: 5.7] [Reference Citation Analysis (0)] |
127. | Tessitore L, Davit A, Sarotto I, Caderni G. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Carcinogenesis. 2000;21:1619-1622. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 35] [Cited by in F6Publishing: 35] [Article Influence: 1.5] [Reference Citation Analysis (0)] |