• Neoplasms
• Phosphatidylinositol 3-kinase signal transduction
• Proto-oncogene protein Akt
• Resveratrol

• age-related CRC
• colorectal cancer
• elderly patients
• molecular targets
• polyphenols

• Humans
• Polyphenols/therapeutic use
• Polyphenols/pharmacology
• Polyphenols/administration & dosage
• Colorectal Neoplasms/prevention & control
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/drug therapy
• Aged
• Animals

• Angiogenesis
• Anti-proliferation
• Diethylnitrosamine
• Hepatocellular carcinoma
• Hongjam
• Thioacetamide

• Apoptosis
• Cancer stem cells
• Colorectal cancer
• Epithelial-mesenchymal transition
• Inflammation
• P53
• Resveratrol
• Tumor cell plasticity

• Humans
• Resveratrol/pharmacology
• Tumor Suppressor Protein p53/metabolism
• Apoptosis/drug effects
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Epithelial-Mesenchymal Transition/drug effects
• Signal Transduction/drug effects
• Animals
• Cell Plasticity/drug effects
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/drug effects

• Acacia concinna
• KRAS mutant
• apoptosis
• colon cancer

• Humans
• Apoptosis/drug effects
• HCT116 Cells
• Endoplasmic Reticulum Stress/drug effects
• Plant Extracts/pharmacology
• Acacia/chemistry
• Signal Transduction/drug effects
• Reactive Oxygen Species/metabolism
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/metabolism
• Colonic Neoplasms/pathology
• Membrane Potential, Mitochondrial/drug effects
• Cell Proliferation/drug effects
• Proto-Oncogene Proteins c-akt/metabolism

• NRCT5-RGJ63017-152 National Research Council of Thailand (NRCT)
• 405/2564 Research Division, Faculty of Medicine, Srinakharinwirot University
• 377/2565 the Strategic Wisdom and Research Institute, Srinakharinwirot University

• analogs
• colorectal cancer
• multidrug resistance
• resveratrol
• tumor microenvironment

• Humans
• Resveratrol/pharmacology
• Colorectal Neoplasms/drug therapy
• Tumor Microenvironment/drug effects
• Antineoplastic Agents, Phytogenic/pharmacology
• Stilbenes/pharmacology
• Signal Transduction/drug effects

• Humans
• DNA Methylation/drug effects
• Colorectal Neoplasms/prevention & control
• Colorectal Neoplasms/genetics
• Stilbenes/pharmacology
• Epigenesis, Genetic
• Animals
• Phytochemicals/pharmacology
• Phytochemicals/therapeutic use

• Alternative splicing
• Gastric cancer
• MAGOH
• PI3K/AKT signaling pathway
• RONΔ160
• hnRNPA1

• Humans
• Nuclear Proteins
• Phosphatidylinositol 3-Kinases
• Proteomics
• Proto-Oncogene Proteins c-akt
• RNA
• RNA, Messenger
• Signal Transduction
• Stomach Neoplasms/genetics

• No. 2020C03112 Key Research and Development Program of Zhejiang Province
• No. 82072631 National Natural Science Foundation of China

• Cancer
• chemotherapeutic treatments.
• drug
• flavonoid
• resveratrol
• signaling pathways

• Resveratrol/pharmacology
• Resveratrol/therapeutic use
• Humans
• Animals
• Antineoplastic Agents, Phytogenic/therapeutic use
• Antineoplastic Agents, Phytogenic/pharmacology
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/pathology
• Carcinoma/drug therapy
• Carcinoma/metabolism
• Carcinoma/pathology

• chemopreventive compounds
• colorectal cancer
• molecular pathways

• colorectal cancer
• epigenetics
• histone deacetylation and acetylation
• histone methylation and demethylation
• histone modification
• histone phosphorylation
• natural products

• 2020M670825 and 2020T130568 China Postdoctoral Science Foundation
• 20210204013YY, and 20230401062YY Jilin Province Science and Technology Development Project in China
• 202210199004 and 202210199011X National College Students' innovation and entrepreneurship training pro-gram
• 82003985 National Natural Science Foundation of China

• APC
• CRC therapy
• Wnt pathway
• colorectal carcinogenesis

Multiple studies investigating the relationship between intake of different types of fruit and colorectal cancer (CRC) risk have yielded inconsistent results.

To perform a meta-analysis of existing studies to assess the association between the intake of different kinds of fruit and the incidence of CRC.

We searched online literature databases including PubMed, Embase, WOS, and Cochrane Library for relevant articles available up to August 2022. With data extracted from observational studies, odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using random-effects models. A funnel plot and Egger’s test were used to determine publication bias. Furthermore, subgroup analysis and dose-response analysis were performed. All analyses were conducted using R (version 4.1.3).

Twenty-four eligible studies involving 1068158 participants were included in this review. The meta-analysis showed that compared to a low intake, a higher intake of citrus, apples, watermelon, and kiwi reduced the risk of CRC by 9% [OR (95%CI) = 0.91 (0.85-0.97)], 25% [OR (95%CI) = 0.75 (0.66-0.85)], 26% [OR (95%CI) = 0.74 (0.58-0.94)], 13% [OR (95%CI) = 0.87 (0.78-0.96)], respectively. No significant association was observed between the intake of other types of fruit and the risk of CRC. In the dose-response analysis, a nonlinear association was found [R (95%CI) = -0.0031 (-0.0047 to -0.0014)] between citrus intake and CRC risk (P < 0.001), with the risk minimized around 120 g/d (OR = 0.85), while no significant dose-response correlation was observed after continued increase in intake.

We found that a higher intake of citrus, apples, watermelon, and kiwi was negatively associated with the risk of CRC, while the intake of other types of fruits were not significantly associated with CRC. Citrus intake showed a non-linear dose-response relationship with the risk of CRC. This meta-analysis provides further evidence that a higher intake of specific types of fruit is effective in preventing the occurrence of CRC.

• Colorectal cancer
• Fruit
• Dose
• Systematic review
• Meta-analysis

• Fruit
• Diet/adverse effects
• Risk Factors
• Citrus
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/prevention & control

• Chung-Ang University
• National Research Foundation of Korea

• cancer risk factor
• flavonoids
• lignans
• natural products
• phenols
• phosphorylation
• prognosis

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural phenol that is present in the skin of the grape, blueberry, raspberry, mulberry, and peanut. This substance is synthesized in these plants following injury or exposure to pathogens. Resveratrol is used as a dietary supplement for a long time and its effects have been assessed in animal models of human disorders. It has potential beneficial effects in diverse pathological conditions such as diabetes mellitus, obesity, hypertension, neoplastic conditions, Alzheimer's disease, and cardiovascular disorders. Notably, resveratrol has been found to affect the expression of several genes including cytokine coding genes, caspases, matrix metalloproteinases, adhesion molecules, and growth factors. Moreover, it can modulate the activity of several signaling pathways such as PI3K/AKT, Wnt, NF-κB, and Notch pathways. In the current review, we summarize the results of studies that reported modulatory effects of resveratrol on the expression of genes and the activity of signaling pathways. We explain these results in two distinct sections of non-neoplastic and neoplastic conditions.

• Gene expression
• NF-κB
• Notch
• PI3K/AKT pathway
• Resveratrol

• colorectal cancer
• flavonoids
• natural compounds
• polyphenol
• signaling pathway

• Department of Science and Technology of Jilin Province
• Jilin Province Development and Reform Commission
• Education Department of Jilin Province
• Jilin Engineering Normal University

• Gastrointestinal cancer
• Nanoformulation
• Resveratrol
• Therapy

Colorectal cancer (CRC) is an emerging public health problem and the second leading cause of death worldwide, with a significant socioeconomic impact in several countries. The 5-year survival rate is only 12% due to the lack of early diagnosis and resistance to available treatments, and the canonical Wnt signaling pathway is involved in this process. This review underlines the importance of understanding the fundamental roles of this pathway in physiological and pathological contexts and analyzes the use of naturally occurring small molecules that inhibits the Wnt/β-catenin pathway in experimental models of CRC. We also discuss the progress and challenges of moving these small molecules off the laboratory bench into the clinical platform.

Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.

• PTEN
• apoptosis
• cervical cancer
• p53

• Benzo[a]pyrene
• Connexin 43
• Gap junction
• Toxicity
• Wnt
• β-catenin

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn’s disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation.

• biotransformation
• curcumin
• gastrointestinal diseases
• gastroprotective
• polyphenols
• resveratrol

Colon cancer commonly develops from long-term chronic inflammation in the intestine and seriously threatens human health. Natural polyphenols have been valued as a crucial regulator of nutrient metabolism and metabolic diseases, owing to their anti-inflammatory and antioxidant functions and the ability to maintain a balance between gut microbes and their hosts. Notably, experimental and clinical evidence has shown that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of colon cancer. Thus, in this review, we summarized recent advances in the possible regulatory mechanism and the potential application of natural polyphenols in colon cancer, which might be regarded as a novel platform for the colon cancer management.

• colon cancer
• inflammation
• microbe
• natural polyphenols
• targeted modulator

• Cancer
• Cancer stem cells
• In vitro and in vivo studies
• Resistance
• Resveratrol
• Signal transduction
• Therapeutic targeting

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.

• Gastrointestinal cancer
• Resveratrol
• Function
• Molecular mechanisms
• Prevention
• Treatment

• Breast cancer
• MicroRNA
• Wnt/β-catenin signaling

• FNDC3B
• PI3K/mTOR
• colorectal cancer
• invasion
• microRNA
• proliferation

• Akt
• B cells
• BAFF
• Ca(2+)
• Erk1/2
• PTEN
• Rapamycin
• mTORC1/2

• PI3K/Akt/mTOR
• cytokines
• radiation
• resveratrol

• Animals
• Anti-Inflammatory Agents/pharmacology
• Gamma Rays
• Inflammation
• Intestines/immunology
• Intestines/radiation effects
• Male
• NF-kappa B/metabolism
• Oxidative Stress/immunology
• Oxidative Stress/radiation effects
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Radiation Injuries, Experimental/immunology
• Radiation Injuries, Experimental/metabolism
• Radiation Injuries, Experimental/prevention & control
• Rats
• Resveratrol/pharmacology
• Signal Transduction/drug effects
• TOR Serine-Threonine Kinases/metabolism
• Tumor Necrosis Factor-alpha/metabolism

• Colorectal cancer
• EGFR
• MAPK
• Notch
• TGF-β

• CRC pathogenesis
• PI3K/AKT signaling
• colorectal cancer
• microRNAs
• microrna
• tumor suppressor.

• Colorectal cancer
• Murine models
• Pristimerin
• Wnt/β-catenin

Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.

MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone.

The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation.

These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19.

Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2.

• Angelica polysaccharide
• Long non-coding RNA H19
• Osteoporosis
• Phosphatidylinositol 3-kinase/protein kinase B
• Wnt/β-catenin

• Adenylate cyclase
• Colon cancer
• Guanylate cyclase
• Phosphodiesterases
• cAMP
• cGMP

Background: Colorectal cancer (CRC) is a common form of cancer associated with a high mortality rate and poor prognosis. Given the limited efficacy of current therapies for CRC, interest in novel therapeutic agents isolated from natural sources has increased. We studied the anticancer properties of isobavachalcone (IBC), a flavonoid isolated from the herb Psoralea corylifolia, which is used in traditional Chinese medicine, in an in vitro model of CRC.

Materials and methods: Cell viability and growth of CRC cells were determined by Cell Counting Kit-8 and colony formation assays following treatment with varying concentrations of IBC, respectively. Apoptosis was examined by 4′,6-diamidino-2-phenylindole staining and flow cytometry with Annexin V/propidium iodide double staining. Western blot analysis was used to analyze expression of apoptosis-associated protein pathway and the AKT/GSK-3β/β-catenin signaling pathway.

Results: Initial experiments showed that IBC inhibited proliferation and colony formation of human CRC cell lines in dose- and time-dependent manners. The antiproliferative effect of IBC resulted from induction of apoptosis, as evidenced by morphological changes in the nucleus, flow cytometry analysis, upregulation of cleaved caspase-3 and cleaved PARP, changes in the ratio of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, translocation of Bax from the cytosol to the mitochondria, and decreased expression of two inhibitors of apoptosis family proteins, XIAP, and survivin. Western blot analysis of signaling pathway proteins demonstrated that IBC downregulated Wnt/β-catenin signaling, which has previously been associated with CRC, by inhibiting the AKT/GSK-3β signaling pathway.

Conclusion: This study demonstrated that IBC inhibited cell proliferation and induced apoptosis through inhibition of the AKT/GSK-3β/β-catenin pathway in CRC. These results suggest the potential of IBC as a novel therapeutic agent for the treatment of CRC.

• AKT
• GSK-3β
• apoptosis
• colorectal cancer
• isobavachalcone
• β-catenin signaling

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach – based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer – has been recently employed to develop ω-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer ω-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs. The aim of this strategy was to increase the activities of the compounds contained in the nanoformulation and to reduce the adverse effects often induced by drugs. We herein analyze the results of papers evaluating the potential use of ω-3 PUFA-containing nanomaterials in fighting cardiovascular diseases and cancer. Future directions in this field of research are also provided.

• cancer
• cardiovascular diseases
• innovative biotechnologies
• nanoparticles
• ω-3 PUFAs

Mounting evidence indicates that microRNAs play important roles in the development of various cancers. Aberrant expression of microRNA-199a-5p has been frequently reported in cancer studies; however, the mechanistic details of the role of microRNA-199a-5p in colorectal cancer still remain unclear. Our study aimed to explore the role of microRNA-199a-5p in colorectal cancer cells by targeting Rho-associated coiled coil-containing protein kinase 1. Here, we showed that microRNA-199a-5p was significantly downregulated in colorectal cancer cell lines and tissue samples and was associated with a poor prognostic phenotype. MicroRNA-199a-5p suppressed colorectal cancer cell proliferation, migration, and invasion and induced cell apoptosis. Moreover, we identified Rho-associated coiled coil-containing protein kinase 1 as the direct target of microRNA-199a-5p using luciferase and Western blot assays. Importantly, Rho-associated coiled coil-containing protein kinase 1 overexpression rescued the microRNA-199a-5p-induced suppression of proliferation, migration, and invasion of colorectal cancer cells. Furthermore, the overexpression of microRNA-199a-5p inhibited tumor growth and metastasis by inactivating the phosphoinositide 3-kinase/AKT and Janus kinase 1/signal transducing activator of transcription signaling pathways through downregulation of Rho-associated coiled coil-containing protein kinase 1. Altogether, microRNA-199a-5p/Rho-associated coiled coil-containing protein kinase 1 may be a potential therapeutic target for colorectal cancer therapy.

• ROCK1
• cell apoptosis
• colorectal cancer
• miR-199a-5p
• progression

• CRC
• Cell cycle
• NVD
• Vitamin D
• Wnt/β-catenin

Numerous studies have demonstrated that PABPC1 participates in the process of carcinogenesis and its function is inconsistent in different types of cancers. PABPC1-like (PABPC1L) is an important paralog of PABPC1 and few studies are available on the roles of PABPC1L in colorectal cancer (CRC) development. Hence, we explored the biological function and prognostic impact of PABPC1L in CRC. The mRNA expression of PABPC1L in CRC was determined based on the data obtained from The Cancer Genome Atlas (TCGA) database. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to determine the PABPC1L mRNA expression level in CRC HT-29 and LS-174T cell lines. Kaplan-Meier method and Cox proportional-hazards model were utilized to conduct the survival and prognosis analyses. HT-29 cells with silenced PABPC1L were constructed to explore the effect of PABPC1L on cell proliferation, invasion and migration capacities using cell counting kit-8 (CCK-8), clone formation, wound-healing and Transwell assays, respectively. To uncover the potential mechanisms of how PABPC1L influences CRC proliferation and migration, we analyzed the expression of AKT, p-AKT, PI3K, and p-PI3K in HT-29 cells using western blotting. Our results revealed that PABPC1L was overexpressed in CRC tissues compared with normal tissues based on the data obtained from TCGA database. Similarly, the mRNA expression of PABPC1L was higher in HT-29 and LS-174T cells than that in CCD-18Co cells. The expression of PABPC1L in CRC was found to be significantly related to age, pathologic stage, pathologic-node, pathologic-metastasis, and death. In univariate and multivariate analyses, pathologic-tumor and pathologic-metastasis were identified as independent prognostic factors for CRC. After PABPC1L depletion, cell proliferation rate, colony numbers, and the invasive and migratory capacity of HT-29 cells were all reduced. Western blot analysis showed that reduction of PABPC1L significantly inhibited p-AKT, and p-PI3K expression level in HT-29 cells. Collectively, our results suggested that PABPC1L is a potential novel candidate oncogene in CRC, and targeting PABPC1L may provide clinical utility in CRC.

• PABPC1L
• cell proliferation
• colorectal cancer
• migration

• collagen induced arthritis
• resveratrol
• rheumatoid arthritis

• Administration, Oral
• Animals
• Anti-Inflammatory Agents/pharmacology
• Arthritis, Experimental/drug therapy
• Arthritis, Experimental/genetics
• Arthritis, Experimental/immunology
• Arthritis, Experimental/pathology
• Bone and Bones/drug effects
• Bone and Bones/immunology
• Bone and Bones/pathology
• Cartilage/drug effects
• Cartilage/immunology
• Cartilage/pathology
• Drug Administration Schedule
• Female
• Gene Expression Regulation
• Hindlimb
• Inflammation
• Mitogen-Activated Protein Kinase 3/genetics
• Mitogen-Activated Protein Kinase 3/immunology
• Rats
• Rats, Wistar
• Resveratrol/pharmacology
• STAT3 Transcription Factor/antagonists & inhibitors
• STAT3 Transcription Factor/genetics
• STAT3 Transcription Factor/immunology
• Wnt Signaling Pathway/drug effects
• Wnt-5a Protein/genetics
• Wnt-5a Protein/immunology
• src-Family Kinases/antagonists & inhibitors
• src-Family Kinases/genetics
• src-Family Kinases/immunology

• Dietary phytochemicals
• clinical study
• colorectal cancer
• epigenetic regulators
• microbiota
• molecular targets
• preclinical study
• signaling pathways

New approaches for the prevention of colon cancer perseveres an essential necessity. Though, resistance to existing chemo-preventive drugs is moderately predominant in colon carcinogenesis. Taxifolin (dihydroquercetin) is a flavononol, have shown virile biological activities against few cancers. The current study was designed to investigate and equate antitumor activity of Taxifolin (TAX) in colorectal cancer cell lines and in HCT116 xenograft model in a comprehensive approach.

Two human colorectal cancer cell lines HCT116 and HT29, were used. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MMT) protocol was performed to elucidate the impact of TAX and β- catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis /cell cycle assay was performed. Data interpretation was done with a FACScan (Becton Dickinson, NJ). About 1 × 10⁴ cells per sample were harvested. Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo.

We found that TAX induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that administration of TAX to human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, variation in molecules controlling cell cycle operative in the G2 phase of the cell cycle and apoptosis in a concentration dependent approach. Further our results concluded that TAX administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo.

Our findings proposed that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.

The online version of this article (10.1186/s12885-018-4959-4) contains supplementary material, which is available to authorized users.

• Colorectal cancer
• Taxifolin and cell cycle
• Wnt/ β-catenin

• Different malignancy cancer cells
• Indirect co-culture
• Invasiveness
• Mesenchymal stem cells
• PTBP1

• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Coculture Techniques
• Female
• Gene Expression
• Gene Silencing
• HCT116 Cells
• HT29 Cells
• Heterogeneous-Nuclear Ribonucleoproteins/genetics
• Heterogeneous-Nuclear Ribonucleoproteins/metabolism
• Humans
• Interferon Type I/metabolism
• Mesenchymal Stem Cells/metabolism
• Mice
• Paracrine Communication
• Polypyrimidine Tract-Binding Protein/genetics
• Polypyrimidine Tract-Binding Protein/metabolism
• RNA, Small Interfering/genetics
• STAT1 Transcription Factor
• Signal Transduction

• Erk1/2
• PP2A
• PTEN
• cell adhesion
• resveratrol