title: Long term effect of curcumin in regulation of glycolytic pathway and angiogenesis via modulation of stress activated genes in prevention of cancer.
abstract: Oxidative stress, an important factor in modulation of glycolytic pathway and induction of stress activated genes, is further augmented due to reduced antioxidant defense system, which promotes cancer progression via inducing angiogenesis. Curcumin, a naturally occurring chemopreventive phytochemical, is reported to inhibit carcinogenesis in various experimental animal models. However, the underlying mechanism involved in anticarcinogenic action of curcumin due to its long term effect is still to be reported because of its rapid metabolism, although metabolites are accumulated in tissues and remain for a longer time. Therefore, the long term effect of curcumin needs thorough investigation. The present study aimed to analyze the anticarcinogenic action of curcumin in liver, even after withdrawal of treatment in Dalton's lymphoma bearing mice. Oxidative stress observed during lymphoma progression reduced antioxidant enzyme activities, and induced angiogenesis as well as activation of early stress activated genes and glycolytic pathway. Curcumin treatment resulted in activation of antioxidant enzyme super oxide dismutase and down regulation of ROS level as well as activity of ROS producing enzyme NADPH:oxidase, expression of stress activated genes HIF-1α, cMyc and LDH activity towards normal level. Further, it lead to significant inhibition of angiogenesis, observed via MMPs activity, PKCα and VEGF level, as well as by matrigel plug assay. Thus findings of this study conclude that the long term effect of curcumin shows anticarcinogenic potential via induction of antioxidant defense system and inhibition of angiogenesis via down regulation of stress activated genes and glycolytic pathway in liver of lymphoma bearing mice.
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Department of Zoology (Centre of Advanced Study), Banaras Hindu University, Varanasi, India.
authors.forename: Laxmidhar
authors.initials: L
authors.lastname: Das
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Department of Zoology (Centre of Advanced Study), Banaras Hindu University, Varanasi, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Vinayak
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001711:Biotransformation; D003094:Collagen; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D015536:Down-Regulation; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects* / Q000235:genetics; D007797:Laminin; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011509:Proteoglycans; D011897:Random Allocation
chemical_list: D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D003474:Curcumin