Our previous study indicated that α-conidendrin had considerable anti-proliferative activities against breast cancer cell lines. The present study aimed to evaluate the anti-colon cancer and anti-angiogenic influences of α-conidendrin as well as its molecular mechanisms. The findings of the current study demonstrate that α-conidendrin possesses potent anti-colon cancer and anti-angiogenic effects. α-Conidendrin significantly inhibited the proliferation of colon cancer cells. This polyphenolic compound induced caspase-mediated apoptosis in HT-29 cells by modulating the PTEN/PI3K/Akt/mTOR signaling pathway. α-Conidendrin markedly upregulated the protein expression of PTEN and downregulated the protein expression of p-PI3K, p-AKt, and p-mTOR. The protein expression of caspase-3 and caspase-9 enhanced in colon cancer cells following treatment with α-conidendrin. This study also revealed the anti-angiogenic activities of α-conidendrin in the ex vivo and in vitro models. α-Conidendrin significantly downregulated the mRNA expression of HIF-1α, VEGF, MMP-2, and MMP-9 in endothelial cells. These data highlight that α-conidendrin can act as a novel and promising anti-cancer and anti-angiogenic agent for treatment of colon cancer.

This review examines recent advancements in nanoparticle-based delivery systems for phytochemicals, focusing on their role in overcoming multidrug resistance, improving therapeutic efficacy, and facilitating clinical translation.

This review highlights recent advances in nanoparticle-enabled phytochemical delivery to enhance bioavailability, improve therapeutic outcomes, and enable targeted applications. By comparing various nanoparticle systems, formulation methods, and efficacy data, it identifies gaps in current research and guides the development of more effective, next-generation phytochemical-loaded nanocarriers.

A systematic review of literature published between 2000 and 2024 was conducted using PubMed, Scopus, and Web of Science. Articles focusing on nanoparticle-based phytochemical delivery in cancer therapy were included.

Compounds such as curcumin, resveratrol, quercetin, and epigallocatechin gallate demonstrate enhanced anti-cancer efficacy when encapsulated in nanoparticles, leading to improved bioavailability, increased tumor cell targeting, and reduced toxicity. Clinical trials indicate tumor regression and fewer adverse effects. Emerging approaches-such as nanogels, hybrid nanoparticles, and combination therapies with immune checkpoint inhibitors-further refine treatment efficacy.

Nanoparticle-based delivery systems significantly improve the therapeutic potential of phytochemicals, making them promising candidates for safer, more effective cancer treatments. However, challenges related to regulatory guidelines, scalability, and long-term safety must be addressed to fully realize their clinical potential.

Despite the recognized neuroprotective benefits of curcumin, its clinical utility is constrained by poor bioavailability and high cytotoxicity at effective doses. This study evaluates the therapeutic potential of curcumin-derived carbon quantum dots (Cur-CQDs) for retinal protection against ischemia-reperfusion (IR) injury in rats. Cur-CQDs were synthesized via mild pyrolysis at varying temperatures and assessed for efficacy in rat retinal ganglion cells and a model of retinal IR injury. The Cur-CQDs, particularly those synthesized at 150 °C, displayed significant reductions in apoptosis in retinal tissues, as indicated by TUNEL assays, immunofluorescence localization of HIF-α, CD68, BCL-2, and Grp78, and Western blot analysis for HO-1, Grp78, CHOP, caspase 3, and Nrf2. These results suggest that Cur-CQDs not only enhance cell survival and reduce inflammation but also decrease oxidative and endoplasmic reticulum stress markers. Mechanistic insights reveal that Cur-CQDs modulate pathways involved in oxidative stress, apoptosis, and inflammation, specifically through the upregulation of BCL-2 and HO-1 and the downregulation of CHOP, caspase-3, and endoplasmic reticulum stress markers. The identification of cinnamic acid-, anisole-, guaiacol, and ferulic acid-like structures on Cur-CQDs' surfaces may contribute to their superior antioxidative and anti-inflammatory activities. Collectively, these findings position Cur-CQDs as a promising approach for treating retinal IR injuries, enhancing curcumin's bioavailability and therapeutic efficacy, and paving new pathways in ocular neuroprotection research and potential clinical applications.

Background and Objective:Mammea siamensis (MS) is a Thai herb used in traditional medicine. Previous studies have reported the antiproliferative effects of its constituents in various cancer cell lines. However, the effects of MS extract on cytotoxicity and molecular mechanisms of apoptosis induction in HCT116 colon cancer cells have not been fully explored. Methods and Results: The cytotoxic effect of MS extract on HCT116 cells was assessed using the MTT assay. MS extract increased cytotoxicity in a concentration-dependent manner. It also induced nuclear morphological changes and disrupted the mitochondrial membrane potential (ΔΨm), as assessed by Hoechst 33342 and JC-1 staining, respectively. These findings indicated that MS extract induced apoptosis, which was further confirmed by flow cytometry showing an increase in the sub-G1 phase. To investigate the expression of signaling proteins, Western blot analysis was conducted. The results showed that MS extract activated caspase activity (caspase-8, -9, and -7) and inhibited PARP activity. Additionally, MS extract upregulated pro-apoptotic proteins (tBid, Bak, and cytochrome c) while downregulating anti-apoptotic proteins (Bcl-2 and Bcl-xL). Mechanistic studies revealed that MS extract activated MAPK pathways while inactivating the PI3K/Akt/NF-κB and GSK-3β/β-catenin pathways. Notably, MS extract also inhibited V-ATPases, as evaluated by acridine orange staining and Western blot analysis. Conclusions: Our findings suggest that MS extract induces apoptosis via the activation of both intrinsic and extrinsic pathways associated with the key signaling pathways. Therefore, MS extract shows potential as a therapeutic agent for colon cancer.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.

Pithecellobium dulce (P. dulce) is a Mexican plant that is consumed raw or in different preparations, and its anti-inflammatory and antioxidant properties have traditionally been useful in treating several conditions. However, the post-harvest drying process can alter the content of bioactive compounds in P. dulce. This study aims to evaluate the impact of different drying methods on the phenolic profile and antioxidant capacity of this plant, as well as its inhibitory effect on human SW480 colon adenocarcinoma cells. After oven drying, the samples showed a higher amount (p < 0.05) of phenolic compounds, up to 1149.45 ± 69.27 mg GAE/100 g LE, which is 80% more than the freeze-dried samples. Also, the antioxidant capacity was higher in oven-dried samples, with 44.63 ± 2.00 µmol Trolox equivalents/g LE, 108% more than the freeze-dried method. Methanolic extraction, in turn, yielded better results than aqueous and ethanolic extractions. Up to 14 polyphenolic compounds were detected in oven-dried samples. For in vitro assays in SW480 cells, the 50% v/v methanolic extract was used. From this extract, the median lethal concentration (LC50) was determined to be 13.76 mg/mL, which represents the concentration necessary to inhibit the growth of half of the cancer cells of this cell line. The extract led to cell cycle arrest in the G1 phase and an increase in apoptosis-induced cell death. The P. dulce extract augmented p53 and decreased KRAS gene expressions. Results suggested pro-apoptotic mechanisms in colon cancer cells in vitro linked to P. dulce bioactive compounds, which are better preserved when oven-dried plants are subjected to methanolic extraction.

This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. In-vitro release and anticancer analyses were explored using HT29 cells. Additionally, in-vivo pharmacokinetics study was investigated followed by histopathological examination and in-vivo anticancer analysis. The PS, PDI, ZP, %EE of IRT and %EE of CUR were found to be 136.15 nm, 0.143, -15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. In-vivo antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.

Various ailments have been treated with pineapple (Ananas comosus (L.) Merr.) throughout medicinal history. Pineapple and its bioactive compound bromelain possess health-promoting benefits. Detailed information on the chemotherapeutic activities of pineapple and its bioactive compound bromelain is provided in this review, which analyses the current literature regarding their therapeutic potential in cancer. Research on disease models in cell cultures is the focus of much of the existing research. Several studies have demonstrated the benefits of pineapple extract and bromelain for in vitro and in vivo cancer models. Preliminary animal model results show promise, but they must be translated into the clinical setting. Research on these compounds represents a promising future direction and may be well-tolerated.

Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification.

We systematically searched international databases, including PubMed, Scopus, and Web of Science, until July 2021 by using some relevant keywords.

The search resulted in 87 papers, among which there were 18 related articles. Curcumin was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR-34, miR-126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the downregulation of miR-21, miR-155, miR-221, miR-222, miR-17-5p, miR-130a, miR-27, and miR-20a.

The present review study suggests that curcumin may be useful as a novel therapeutic agent for CRC by altering the expression level of miRs.

Colorectal cancer (CRC) is currently ranked as the third most common type of cancer, contributing significantly to mortality and morbidity worldwide. Epigenetic and genetic changes occurred during CRC progression resulted in the cell proliferation, cancer progression, angiogenesis, and invasion. Angiogenesis is one of the crucial steps during cancer progression required for the delivery of essential nutrients to cancer cells and removes metabolic waste. During angiogenesis, different molecules are secreted from tumoral cells to trigger vascular formation including epidermal growth factor and the vascular endothelial growth factor (VEGF). The production and regulation of the secretion of these molecules are modulated by different subcellular pathways such as NF-κB. NF-κB is involved in regulation of different homeostatic pathways including apoptosis, cell proliferation, inflammation, differentiation, tumor migration, and angiogenesis. Investigation of different aspects of this pathway and its role in angiogenesis could provide a comprehensive overview about the underlying mechanisms and could be used for development of further therapeutic targets. In this review of literature, we comprehensively reviewed the current understanding and potential of NF-κB-related angiogenesis in CRC. Moreover, we explored the treatments that are based on the NF-κB pathway.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printed calcium phosphate (CaP) scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127 nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Breast cancer (BC) bone metastasis poses a significant clinical challenge due to its impact on patient prognosis and quality of life. Curcumin (CUR), a natural polyphenol compound found in turmeric, has shown potential in cancer therapy due to its anti-inflammatory, antioxidant, and anticancer properties. However, its metabolic instability and hydrophobicity have hindered its clinical applications, leading to a short plasma half-life, poor absorption, and low bioavailability. To enhance the drug-like properties of CUR, nanotechnology-based delivery strategies have been employed, utilizing polymeric, lipidic, and inorganic nanoparticles (NPs). These approaches have effectively overcome CUR's inherent limitations by enhancing its stability and cellular bioavailability both in vitro and in vivo. Moreover, targeting molecules with high selectivity towards bone metastasized breast cancer cells can be used for site specific delivery of curcumin. Alendronate (ALN), a bone-seeking bisphosphonate, is one such moiety with high selectivity towards bone and thus can be effectively used for targeted delivery of curcumin loaded nanocarriers. This review will detail the process of bone metastasis in BC, elucidate the mechanism of action of CUR, and assess the efficacy of nanotechnology-based strategies for CUR delivery. Specifically, it will focus on how these strategies enhance CUR's stability and improve targeted delivery approaches in the treatment of BC bone metastasis.

Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.

Aging is a multifaceted process influenced by hereditary factors, lifestyle, and environmental elements. As time progresses, the human body experiences degenerative changes in major functions. The external and internal signs of aging manifest in various ways, including skin dryness, wrinkles, musculoskeletal disorders, cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. Additionally, cancer, like aging, is a complex disease that arises from the accumulation of various genetic and epigenetic alterations. Circadian clock dysregulation has recently been identified as an important risk factor for aging and cancer development. Natural compounds and herbal medicines have gained significant attention for their potential in preventing age-related diseases and inhibiting cancer progression. These compounds demonstrate antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic effects as well as circadian clock regulation. This review explores age-related diseases, cancers, and the potential of specific natural compounds in targeting the key features of these conditions.

Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis-resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost-effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co-therapeutic agent in CRC.

Colorectal cancer (CRC) remains a significant global health concern, being the third most diagnosed cancer in men and the second most diagnosed cancer in women, with alarming mortality rates. Natural phytochemicals have gained prominence among various therapeutic avenues explored due to their diverse biological properties. Curcumin, extracted from turmeric, and resveratrol, a polyphenol found in several plants, have exhibited remarkable anticancer activities. However, their limited solubility and bioavailability hinder their therapeutic efficacy. To enhance the bioavailability of these compounds, nanomaterials work as effective carriers with biogenic silica (BS) attracting major attention owing to their exceptional biocompatibility and high specific surface area. In this study, we developed Curcumin-resveratrol-loaded BS (Cur-Res-BS) and investigated their effects on colorectal cancer cell lines (HCT-116 and Caco-2). Our results demonstrated significant concentration-dependent inhibition of cell viability in HCT-116 cells and revealed a complex interplay of crucial proto-onco or tumor suppressor genes, such as TP53, Bax, Wnt-1, and CTNNB1, which are commonly dysregulated in colorectal cancer. Notably, Cur-Res-BS exhibited a synergistic impact on key signaling pathways related to colorectal carcinogenesis. While these findings are promising, further investigations are essential to comprehensively understand the mechanisms and optimize the therapeutic strategy. Moreover, rigorous safety assessments and in vitro studies mimicking the in vivo environment are imperative before advancing to in vivo experiments, ensuring the potential of Cur-Res-BS as an efficient treatment for CRC.

Curcumin is a natural compound that has been widely investigated thanks to its various biological properties, including antiproliferative. This molecule acts on different cancers such as lung, breast, pancreatic, colorectal, etc. However, the bioactive actions of curcumin have limitations when its physicochemical properties compromise its pharmacological potential. As a therapeutic strategy against cancer, curcumin has been associated with inorganic nanoparticles. These nanocarriers are capable of delivering curcumin and offering physicochemical properties that synergistically enhance anticancer properties. This review highlights the different types of curcumin-based inorganic nanoparticles and discusses their physicochemical properties and in vivo anticancer activity in different models of cancer.

Colorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial.

In this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria.

Our results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway.

In conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.

Colorectal cancer (CRC) is the main cause of cancer-associated death. Herein, we treated SW620 and HT-29 CRC cells with different curcumin concentrations, followed by treatment with the half maximal inhibitory concentration (IC50) curcumin/endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA)/activating transcription factor 6 (ATF6) interference plasmid (si-ATF6). We detected cell proliferation/apoptosis, ATF6 cellular localization/nuclear translocation, ion concentration, ATF6 protein/apoptotic protein (Bax/Bcl-2/Cleaved Caspase-3) levels, and ERS-related proteins (glucose-regulated protein 78 [Grp78]/C/EBP homologous protein [CHOP]). We discovered inhibited cell proliferation/growth, enhanced cell apoptosis/(Bax/Bcl-2) ratio/Cleaved Caspase-3 levels/Ca2+ concentration in the cytoplasm/ERS-related protein (Grp78/CHOP) levels, and activated ERS following treatment with IC50 curcumin. 4-PBA partially reversed the inhibitory effect of curcumin on SW620 cells by restraining ERS. Curcumin stimulated ATF6 expression and its nuclear translocation to activate ERS. ATF6 silencing partly annulled the inhibitory effect of curcumin on SW620 cells. Our study explored the molecular mechanism of curcumin affecting CRC cell apoptosis through ATF6.

This study investigate the anti-tumor effect of curcumin and whether its mediated by hsa_circ_0136666 through miR-1301-3p/CXCL1 in colorectal carcinoma (CRC). Through multiple experiments, we have drawn the conclusion that curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis, hinting at a novel treatment option for curcumin to prevent CRC development.

To determine whether hsa_circ_0136666 involvement in curcumin-triggered CRC progression was mediated by sponging miR-1301-3p.

Cell counting kit-8, colony-forming cell, 5-ethynyl-2'-deoxyuridine, and flow cytometry assays were carried out to determine cell proliferation, apoptosis, and cell cycle progression. Real-time quantitative polymerase chain reaction quantified hsa_circ_0136666, miR-1301-3p, and chemokine (C-X-C motif) ligand 1 (CXCL1), and western blot analysis determined CXCL1, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) protein levels. CircBank or starbase software was first used for the prediction of miR-1301-3p binding with hsa_circ_0136666 and CXCL1, followed by RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assay validation. In vivo experiments were implemented in a murine xenograft model.

Curcumin blocked CRC cell proliferation but boosted apoptosis. Moreover, elevated hsa_circ_0136666 Levels were observed in CRC cells, which were reduced by curcumin. In vitro, hsa_circ_0136666 overexpression abolished the antitumor activity of CRC cells. Mechanical analysis revealed the ability of hsa_circ_0136666 to sponge miR-1301-3p to modulate CXCL1 levels.

Curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis, hinting at a novel treatment option for curcumin to prevent CRC development.

Colorectal cancer is still unmanageable despite advances in target therapy. However, extracellular vesicles (EVs) have shown potential in nanomedicine as drug delivery systems, especially for modulating the immune cells in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), alone or in combination (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines and prevent metastasis in mice of allograft and peritoneal colorectal cancer models. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or particularly M1EV4 downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastasis in the peritoneum, liver, and lungs. STAT3, NF-kB, and AKT were the major genes downregulated by of M1EV systems. Tumor-associated macrophages (TAMs) shifted from an M2 phenotype (CD163) to an M1 phenotype (CD68) reducing levels of IL-10, TGF-β and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR1, survivin, vimentin, and PD-L1 after treatment with systems of M1EVs. The study shows that EVs from M1 antitumor macrophages can transport drugs and enhance their immunomodulatory and antitumor activity by modulating pathways associated with cell proliferation, migration, survival, and drug resistance.

Curcumin is a bioactive component with anticancer characteristics; nevertheless, it has poor solubility and fast metabolism, resulting in low bioavailability and so restricting its application. Curcumin loaded in nano emulsions (Cur-NE) was developed to improve water solubility and eliminate all the limitations of curcumin. Size distribution, zeta potential, transmission electron microscopy (TEM) measurements, UV-Visible spectra, IR spectra and thermogravimetric analysis (TGA), were used to characterize the prepared Cur-NE. Cancer therapeutic efficacy was assessed by oxidative stress (superoxide dismutase (SOD), Glutathione-S-Transferase (GST), malondialdehyde (MDA) and nitric oxide (NO), DNA damage, apoptotic proteins (caspase-3 and 9), besides investigating tumor histology and monitoring tumor growth. Additionally, the cytotoxicity and genotoxicity of the liver, kidney, heart, and spleen tissues were examined to gauge the adverse effects of the treatment method's toxicity. The results showed that Cur-NE is more effective than free curcumin at slowing the growth of Ehrlich tumors while significantly increasing the levels of apoptotic proteins. On the other hand, Cur-NE-treated mice showed some damage in other organs when compared to mice treated with free curcumin. Cur-NE has a higher efficacy in treating Ehrlich tumor.

The fatal amplification of lung cancer across the globe and the limitations of current treatment strategies emphasize the necessity for substitute therapeutics. The incorporation of phyto-derived components in chemo treatment holds promise in addressing those challenges. Despite the significant progressions in lung cancer therapeutics, the complexities of molecular mechanism and pathways underlying this disease remain inadequately understood, necessitating novel biomarker targeting. The Himalayas, abundant in diverse plant varieties with established chemotherapeutic potential, presents a promising avenue for investigating potential cures for lung carcinoma. The vast diversity of phytocompounds herein can be explored for targeting the disease. This review delves into the multifaceted targets of lung cancer and explores the established phytochemicals with their specific molecular targets. It emphasizes comprehending the intricate pathways that govern effective therapeutic interventions for lung cancer. Through this exploration of Himalayan flora, this review seeks to illuminate potential breakthroughs in lung cancer management using natural compounds. The amalgamation of Himalayan plant-derived compounds with cautiously designed combined therapeutic approaches such as nanocarrier-mediated drug delivery and synergistic therapy offers an opportunity to redefine the boundaries of lung cancer treatment by reducing the drug resistance and side effects and enabling an effective targeted delivery of drugs. Furthermore, additional studies are obligatory to understand the possible derivation of natural compounds used in current lung cancer treatment from plant species within the Himalayan region.

Background: Gastric cancer stands as a primary cause of cancer-related deaths worldwide, making the discovery of new therapeutic agents essential for enhancing treatment outcomes. Curcumin, a polyphenolic compound found in turmeric (Curcuma longa), has demonstrated potential in multiple cancer types due to its anti-cancer characteristics. This research aimed to examine the impact of curcumin on gastric cancer cell growth, migration, and invasion, as well as its influence on the phosphoinositide 3-kinase (PI3K) signaling cascade. Methods: Gastric cancer cell lines were exposed to varying curcumin concentrations, followed by assessments of cell viability, migration, and invasion. Furthermore, gene and protein expression levels associated with the PI3K signaling cascade were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: The findings revealed a dose-dependent decrease in cell viability, migration, and invasion in gastric cancer cells treated with curcumin. Additionally, curcumin administration led to the downregulation of key genes and proteins within the PI3K signaling process, such as PI3K, Akt, and mTOR. Conclusion: These findings propose that curcumin may exercise its anti-cancer effects on gastric cancer cells, partly by suppressing the PI3K signaling pathway. This study's outcomes support curcumin's potential as a therapeutic agent for gastric cancer and encourage further exploration of its underlying molecular mechanisms and in vivo effectiveness.

Colorectal cancer (CRC) is one of the most common causes of death and the third most diagnosed cancer worldwide. The tumor microenvironment and cancer stem cells participate in colorectal tumor progression and can dictate malignancy. Nutrition status affects treatment response and the progression or recurrence of the tumor. This review summarizes the main bioactive compounds against the molecular pathways related to colorectal carcinogenesis. Moreover, we focus on the compounds with chemopreventive properties, mainly polyphenols and carotenoids, which are highly studied dietary bioactive compounds present in major types of food, like vegetables, fruits, and seeds. Their proprieties are antioxidant and gut microbiota modulation, important in the intestine because they decrease reactive oxygen species and inflammation, both principal causes of cancer. These compounds can promote apoptosis and inhibit cell growth, proliferation, and migration. Combined with oncologic treatment, a sensitization to first-line colorectal chemotherapy schemes, such as FOLFOX and FOLFIRI, is observed, making them an attractive and natural support in the oncologic treatment of CRC.

Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation. Recently, increasing evidence in studies shows that pyroptosis has a crucial role in inflammatory conditions like cardiovascular diseases (CVDs), cancer, neurological diseases (NDs), and metabolic diseases (MDs), suggesting that targeting cell death is a potential intervention for the treatment of these inflammatory diseases. Based on this, the review aims to identify the molecular mechanisms and signaling pathways related to pyroptosis activation and summarizes the current insights into the complicated relationship between pyroptosis and multiple human inflammatory diseases (CVDs, cancer, NDs, and MDs). We also discuss a promising novel strategy and method for treating these inflammatory diseases by targeting pyroptosis and focus on the pyroptosis pathway application in clinics.

A series of 5-FU-Curcumin hybrids were synthesized, and their structures were elucidated by spectroscopic analysis. The synthesized hybrid compounds were evaluated in different colorectal cancer cell lines (SW480 and SW620) and in non-malignant cells (HaCaT and CHO-K1), to determine their chemopreventive potential. Hybrids 6a and 6d presented the best IC₅₀ value against the SW480 cell line with results of 17.37 ± 1.16 µM and 2.43 ± 0.33 µM, respectively. Similarly, compounds 6d and 6e presented IC₅₀ results of 7.51 ± 1.47 µM and 14.52 ± 1.31 µM, respectively, against the SW620 cell line. These compounds were more cytotoxic and selective than curcumin alone, the reference drug 5-fluorouracil (5-FU), and the equimolar mixture of curcumin and 5-FU. In addition, hybrids 6a and 6d (in SW480) and compounds 6d and 6e (in SW620) induced cell cycle arrest in S-phase, and, compounds 6d and 6e caused a significant increase in the sub-G0/G1 phase population in both cell lines. Hybrid 6e was also observed to induce apoptosis of SW620 cells with a respective increase in executioner caspases 3 and 7. Taken together, these results suggest that the hybrids could actively act on a colorectal cancer model, making them a privileged scaffold that could be used in future research.

Resistance to cancer radiotherapy is one of the biggest concerns for success in treating and preventing recurrent disease. Malignant tumors may develop when they block genetic mutations associated with apoptosis or abnormal expression of apoptosis; Tumor treatment may induce the expression of apoptosis-related genes to promote tumor cell apoptosis. MicroRNAs have been shown to contribute to forecasting prognosis, distinguishing between cancer subtypes, and affecting treatment outcomes in cancer. Constraining these miRNAs may be an attractive treatment strategy to help overcome radiation resistance. The delivery of these future treatments is still challenging due to the excess downstream targets that each miRNA can control. Understanding the role of miRNAs brings us one step closer to attaining patient treatment and improving patient outcomes. This review summarized the current information on the role of microRNA-induced apoptosis in determining the radiosensitivity of various cancers.

Although concurrent chemoradiotherapy is the cornerstone of treatment for locally advanced or recurrent uterine cervical cancer, treatment fails at a high rate. Therefore, the development of novel targeting agents is critical. This study investigated the action of CLEFMA, a potent, synthetic curcumin derivative, on cervical cancer cells and its mechanism of action. We found that CLEFMA negatively regulated the viability of cervical cancer cells, involving induction of cell apoptosis. Cleaved caspase-3, cleaved poly(adenosine diphosphate-ribose) polymerase, cleaved caspase-8, and cleaved caspase-9 expression were increased by treatment with CLEFMA. After U0126 (ERK1/2 inhibitor) and SB203580 (p38 inhibitor) were applied as cotreatment with CLEFMA, the expression of cleaved caspase-8, -9, and -3 was reduced significantly. In conclusion, CLEFMA activates both extrinsic and intrinsic apoptotic pathways through ERK1/2 and p38 signal transduction in cervical cancer cells.

Gnetum montanum Markgr. (Gnetaceae) is used to treat rheumatic arthralgia and bruises in the clinic.

To exam the activity and mechanism of G. montanum extract (GME) against colon cancer cells SW480.

The anti-proliferative activity of GME (0-120 μg/mL) on SW480 cells was determined using MTS assay at 24, 48, and 72 h. The in vitro activity of GME (0-120 μg/mL) on SW480 cells was investigated using flow cytometry and western blotting analysis. The in vivo activity of GME was evaluated using xenograft tumour model of zebrafish and nude mice. The chemical composition of GME was detected by using HPLC-MS/MS.

The IC₅₀ value SW480 cells viability by GME were 126.50, 78.25, and 50.77 μg/mL, respectively, for 24, 48, and 72 h. The experiments showed that apoptotic cells and G2/M phase cells increased from 20.81 to 61.53% (p < 0.01) and 25.76 to 34.93% with 120 μg/mL GME, respectively. GME also down-regulated the protein expression of P-AKT, P-GSK-3β, P-PDK1, P-c-Raf, caspase-3, and Bcl-2, and up-regulated the expression cleaved caspase-3, cleaved PARP, and Bax. In vivo study found that GME can significantly inhibit the growth and migration of SW480 cells in xenograft zebrafish. GME reduced the nude mice tumour weight to approximately 32.19% at 28 mg/kg/day and to 53.17% (p < 0.01) at 56 mg/kg/day. Forty-two compounds were identified from the GME.

GME has a significant antitumor effect on colon cancer cells SW480, and it has the potential to be developed as an anticancer agent.

5-Fluorouracil (5-FU) is one of the most common chemotherapy drugs used to treat colorectal cancer (CRC), which often develops resistance in more than 15% of patients. Curcumin, an active component of Curcuma longa, has been reported to show antitumor activity in CRC and, furthermore, enhance the effect of chemotherapy against colorectal cancer cells. However, the molecular mechanisms underlying the sensitizing effect of curcumin on 5-FU have not been largely elucidated. In this study, we aimed to systematically investigate the role of curcumin as a chemosensitizer for the treatment of CRC, along with the key events responsible for its pharmaceutical effect, which may lead to better clinical outcomes.

A high-resolution 2DE-based proteomics approach was used to characterize global protein expression patterns in CRC cells treated with 5-FU both in combination with curcumin or without. The differentially expressed proteins were obtained from the 2DE analysis and subsequently identified by MALDI-TOF MS or nano-ESI-MS/MS, some of which were validated by the Western blot. Intracellular reactive oxygen species (ROS) were measured to assess the change in the redox environment resulting from the drug treatment.

A series of proteins with altered abundances were detected and identified by MALDI-TOF or nano-MS/MS. From a total of 512 isolated proteins, 22 proteins were found to be upregulated and 6 proteins were downregulated. Intracellular ROS was significantly elevated after curcumin treatment. Furthermore, mass spectrometry data revealed that some of the proteins appeared to have more oxidized forms upon curcumin treatment, suggesting a direct role for ROS in the chemosensitizing effect of curcumin.

The effect of curcumin in enhancing chemosensitivity to 5-FU is a complex phenomenon made up of several mechanisms, including enhancement of the intracellular level of ROS. Our findings presented here could provide clues for a further study aimed at elucidating the mechanisms underlying the chemosensitizing effect of curcumin.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide and the second cause of cancer-related deaths. It usually starts as an inflammation that progresses to adenocarcinoma. The goal of the present study was to investigate the antitumor efficacy of a new thiophene derivative against CRC in mice and explore the possible associated molecular pathways. The potential of this thiophene derivative to sensitize the CRC tumor tissue to a low dose of gamma irradiation was also investigated.

Adult male mice were divided into seven groups; control, group treated with dimethylhydrazine (DMH) for the induction of CRC. The DMH-group was further divided into six groups and treated with either cisplatin, thiophene derivative, γ-irradiation, cisplatin + γ-irradiation, thiophene derivative + γ-irradiation, or left untreated.

DMH induced CRC as evidenced by the macroscopic examination of colon tissues and histopathology, and elevated the activities of cyclooxygenase2 (COX2) and nitric oxide synthase (iNOS). DMH also elevated kirsten rat sarcoma (KRAS) and downregulated the peroxisome proliferator activated receptor (PPARγ) as shown by RT-PCR and Western blotting. DMH exerted anti-apoptotic activity by reducing the expression of phosphorylated p53 and cleaved caspase3 at the gene and protein levels. The flow cytometry analysis showed that DMH elevated the necrosis and reduced the apoptosis compared to the other groups. The colon tissue from DMH-treated mice showed hyperplasia, aberrant crypt foci, loss of cell polarity, typical CRC of grade 4 with lymphocytes and macrophages infiltrating mucosa, muscularis mucosa, and submucosa score 3. Treatment with thiophene derivative or γ-irradiation ameliorated most of these deleterious effects of DMH. The concomitant action of thiophene derivative + γ-irradiation was typified by the better amelioration of tumor incidence and multiplicity, iNOS, PPARγ, p53, caspase 3, and histopathology of colon.

Taken together, the new thiophene derivative is a promising therapeutic candidate for treatment of colorectal cancer in mice. It also sensitizes the CRC tumor to the ionizing radiation through anti-inflammatory and pro-apoptotic pathways.

Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD.

To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.

Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1β, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins.

After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1β, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice.

Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.

Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [Cmax], area under the curve [AUC], distribution volume [Vd], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured Cmax (n = 27) and AUC (n = 33), and to a lesser extent Vd and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy.

The present study was undertaken to investigate the ability of a drug curcumin-loaded polymer to inhibit the growth of cervical cancer cells by enhancing the anti-cancer efficiency of curcumin. We synthesized poly(methacryloyl beta-alanine) (PMBA) as a nanocarrier by radical polymerization in supercritical CO₂. The results showed that the curcumin encapsulated and folic acid (FA)-treated PMBA (Poly@Cur-FA) for 24 h activated the reactive oxygen species-mediated programmed cell death machinery in HeLa cells. This remarkable effect of Poly@Cur-FA treatment was visualized using different fluorescent probes, which demonstrated that the Poly@Cur-FA treatment disrupted the cell membrane, as also supported by scanning electron microscopy observations. The effect of Poly@Cur-FA dispersion on the cells was observed under a transmission electron microscope. Further, the HeLa cells were treated with the polymer encapsulated curcumin and Bcl2 siRNA (Pol-Cur-siRNA) for 24 h, which effectively suppressed the Bcl2 and simulated the autophagic pathway. This co-delivery system was designed to inhibit curcumin efflux and can enhance the treatment efficacy by targeting multiple signaling pathways, including cell cycle, apoptotic, and autophagic pathways. Collectively, the Pol-Cur-siRNA system appears to offer an efficient combinational therapeutic strategy that might overcome the problems associated with the chemosensitivity against the standard synthetic anti-cancer drugs. To support the experimental data, an artificial neural network model was developed to foresee the drug and gene release behaviors.