title: Morin and Esculetin supplementation modulates c-myc induced energy metabolism and attenuates neoplastic changes in rats challenged with the procarcinogen 1,2 - dimethylhydrazine.
abstract: 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.
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
authors.forename: Sharada H
authors.initials: SH
authors.lastname: Sharma
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Thulasingam
authors.affiliation: Central Animal Facility, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
authors.forename: David Raj
authors.initials: DR
authors.lastname: Chellappan
authors.affiliation: Central Animal Facility, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
authors.forename: Prabu
authors.initials: P
authors.lastname: Chinnaswamy
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India. Electronic address: sangeetha@scbt.sastra.edu.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Nagarajan
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D004734:Energy Metabolism / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D008297:Male; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D047368:Tumor Burden / Q000187:drug effects; D014468:Umbelliferones / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism; D047309:Flavones
chemical_list: D019813:1,2-Dimethylhydrazine; D016588:Anticarcinogenic Agents; D005419:Flavonoids; D016271:Proto-Oncogene Proteins c-myc; D014468:Umbelliferones; D051176:beta Catenin; C008548:morin; D047309:Flavones; C007628:esculetin
keywords: Chemoprevention; Colon cancer; Esculetin; Glutaminolysis; Glycolysis; Morin