morin and Colonic-Neoplasms

The Global cancer incidence and mortality data released by the World Health Organization proposes that out of 18.1 million new cancer cases diagnosed, 9.8 million deaths occurred globally in 2018. Cancer is one of the major health burdens among non-communicable diseases globally responsible for impeding life expectancy in the present century. Disrupting hallmarks of cancer (such as prolonged inflammation, increased growth signal, tissue invasion and metastasis, unlimited proliferation and evasion of apoptosis) with dietary agents is of considerable focus for cancer prevention and therapy. In the last decade, a significant contribution has been provided in finding many plant-derived natural agents that can be identified as promising molecular cancer therapeutics. Our focus in this review is on one such natural dietary agent, Morin (3,5,7,2',4'-pentahydroxyflavone): a bioflavonoid. Morin exerts strong pharmacological properties against a multitude of cancer (liver cancer, cervical cancer, melanoma, breast cancer, prostate, and colon cancer). Recent progress has also been made in examining the potential of morin as a natural dietary agent for fostering the pharmacological effects of other well-known anticancer agents. This review provides an overview of morin and its derivatives in combination with anticancer agents for cancer prevention and therapy.

Topics: Antineoplastic Agents; Apoptosis; Colonic Neoplasms; Flavonoids; Humans; Male

Over the last few decades, the number of people diagnosed with cancer has increased dramatically every year, making it a major cause of mortality today. Colon cancer is the third most common cancer worldwide, and the second in mortality rate. Current cancer treatment fails to treat colon cancer completely due to the remains of Cancer Stem Cells (CSCs). Morin flavonoid present in figs (Ficus carica) and other plant sources, was found to have an anti-proliferative effect on the colon cancer model and cell line, but it is not studied for its effect on the colon CSCs. In this study, we have tested the potency of morin to inhibit CSCs. We found that morin has significantly reduced colon cancer cell proliferation, colony formation, migration, and colonospheroid formation in a dose-dependent manner. Pumilio-1 (PUM1) has been shown to play an important role in colon CSCs maintenance. We found that morin has a good binding affinity with PUM1 protein with one hydrophobic and two hydrogen bond interactions. Further, the immunofluorescence results have also shown a reduction in PUM1 expression in colon cancer cell lines after morin treatment. CD133 is overexpressed in colon CSCs and morin treatment has reduced the CD133 expression in HCT116 and CT26 colon cancer cell lines. Our research outcome has explored the anti-cancer stem cell potency of morin via targeting the PUM1 protein and further reducing the colon spheroids formation and reducing the CD133 expression in colon cancer cells.

Topics: Cell Proliferation; Colonic Neoplasms; Flavones; Flavonoids; Humans; Neoplastic Stem Cells; RNA-Binding Proteins

Topics: Animals; Antioxidants; Carcinogenesis; Colon; Colonic Neoplasms; Disease Models, Animal; Flavonoids; Genes, APC; In Vitro Techniques; Male; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins; Rats; Rats, Inbred F344

Colorectal cancer is the third most common cancer worldwide. The development of effective, inexpensive and safe chemopreventive agents would be of great benefit as it involves use of natural products to prevent or suppress the progression of precursor lesions. Morin a flavonoid found in figs (Ficus carica) and other plants is shown to inhibit 1,2-dimethylhydrazine (DMH) induced colon cancer progression in a short term and long term model of colon cancer rats; however, the molecular target for the colon cancer chemoprotective efficacy of morin is yet to be discovered. The present study aims to explore the molecular basis of how morin contributes to the chemoprevention with a focus on NF-κB signaling pathway. The effect of morin on NF-κB signaling in DMH-induced carcinogenic events such as inflammation and apoptosis were analyzed by studying the histopathological analysis using Hematoxylin and Eosin staining (H &E), mRNA expression using q-PCR, protein expression using Immunohistochemistry (IHC) and western blot. Morin supplementation to DMH administered rats down regulated NF-κB pathway and its downstream inflammatory mediators like tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2) and prostaglandin (PGE-2). Morin supplementation to DMH administered rats alters BAX/BCL2 ratio favoring apoptosis in carcinogen treated rats. Our findings explored that molecular chemoprevention of morin targets NF-κB and acts as a potent anti-inflammatory and pro-apoptotic agent for colon cancer prevention.

Topics: Animals; Antineoplastic Agents, Phytogenic; Chemoprevention; Colonic Neoplasms; Drug Delivery Systems; Flavonoids; Male; NF-kappa B; Random Allocation; Rats; Rats, Wistar

Targeting tumor metabolism by natural products is a novel approach and provides rationale for anti-cancer drug discovery. The present study aims to explore the impact of morin and/or esculetin on c-myc induced energy metabolism in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. In order to achieve this aim we analyzed the expression of glucose and glutamine transporters and the key enzymes of glycolytic pathway besides the markers of neoplastic changes viz., mucin depleted foci (MDF), beta catenin accumulated crypts (BCAC), and markers of cell proliferation viz., proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar antigen (AgNOR), c-myc, c-jun and c-fos. All the parameters tested in the present study are highly influenced by the phytochemicals morin and/or esculetin in a way to prevent colon carcinogenesis. Morin and/or esculetin supplementation effectively targets tumor metabolism via β-cateinin/c-myc signaling and affects glycolysis and glutaminolysis to abrogate colon cancer in rats. The anti-cancer effect of morin is more pronounced than esculetin. The effect obtained through the combined treatment of morin and esculetin is comparable to that of individual supplementation of morin and there is no synergistic effect. Overall individual supplementation of morin scores well as a potential anticancer agent targeting glycolysis and glutaminolysis in colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; beta Catenin; Body Weight; Carcinogenesis; Cell Proliferation; Colon; Colonic Neoplasms; Energy Metabolism; Flavonoids; Glycolysis; Male; Proto-Oncogene Proteins c-myc; Rats; Rats, Wistar; Signal Transduction; Survival Rate; Tumor Burden; Umbelliferones

Chemopreventive agents are used to diminish the morbidity and mortality of cancer by delaying the course of carcinogenesis. Formation of ACF and amplified activity of colon biotransforming enzymes were considered to be hallmarks of colon carcinogenesis. Morin, a bioflavonoid present in fruits and show various pharmacological and biological activities. Our present study, shows the modulatory effect of morin administration on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in rat colon, and fecal and mucosal biotransforming enzyme activities. A total of 64 rats were randomized into four groups. Group 1 served as control, groups 2 and 4 received 50mg/kg b.w. of morin intragastrically for the entire period of the study (30 weeks). Groups 3 and 4 received subcutaneous injection of DMH (20mg/kg b.w.) for 15 weeks. Rats were sacrificed at the end of 30 weeks. The incidence of tumors/polyps in the colon cancer of rats and treated with morin showed reduced incidence (40%) of tumors, as compared to DMH (100%) treated rats. Morin administration significantly reduced ACF formation and lowered the activities of fecal and mucosal biotransforming enzymes. Our findings suggest that morin (50mg/kg b.w.) may be a possible chemopreventive agent against colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; beta-Glucosidase; Carcinogens; Colon; Colonic Neoplasms; Disease Models, Animal; Flavonoids; Glucuronidase; Intestinal Mucosa; Male; Nitroreductases; Polysaccharide-Lyases; Precancerous Conditions; Rats; Rats, Wistar

Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydrazine-induced colon carcinogenesis in a rat model. Male Wistar rats were divided into four groups and received high fat diet. Group 1 served as control, groups 2 and 4 were given a daily treatment of morin (50 mg/kg body weight) orally, everyday for a total period of 30 weeks. Groups 3 and 4 were given weekly subcutaneous injections of DMH at a dose of 20 mg/kg body weight in the groin for 15 weeks. Animals were sacrificed at the end of 30 weeks. The liver, intestine, colon and caecum from different groups were subjected to histopathological studies, determination of lipid peroxidation and antioxidant status. Our results showed decreased levels of liver enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation (LPO) products such as tissue thiobarbituricacid substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) in DMH treated rats, which were significantly (P < 0.05) reversed on morin supplementation. Moreover, intestinal, colonic and caecal TBARS, LOOH, CD and also the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and reduced glutathione (GSH) were significantly diminished in DMH treated rats, which were significantly (P < 0.05) elevated on simultaneous morin supplementation. Moreover, enhanced activity of intestinal, colonic and caecal ascorbic acid and alpha-tocopherol levels were also observed in DMH alone treated rats, which were significantly (P < 0.05) reduced on morin supplementation. These results indicate that morin could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Antioxidants; Cecum; Colonic Neoplasms; Drug Screening Assays, Antitumor; Flavonoids; Intestinal Mucosa; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar