title: Antioxidant α-tocopherol checks lymphoma promotion via regulation of expression of protein kinase C-α and c-Myc genes and glycolytic metabolism.
abstract: Overproduction of reactive oxygen species (ROS) due to environmental challenge or metabolic imbalance leads to oxidative stress, causing overactivation of a number of oncogenes that promote cancer development. Therefore, antioxidants should be able to check cancer growth by modulating oncogene activity. The requirement of high energy during unlimited cell proliferation is fulfilled by the switching of cancerous cells to a fast glycolytic pathway bypassing the oxygen dependent respiratory pathway. Almost all cancers exhibit a high expression of lactate dehydrogenase A (LDH-A) to ensure a high energy supply. The present study focused on modulating redox-sensitive oncogenes such as protein kinase C (PKC) and c-Myc by treatment of lymphoma bearing mice with the antioxidant α-tocopherol, the most active component of vitamin E. Further, the impact of α-tocopherol on LDH activity was tested. The results showed down-regulation of expression of stress-activated genes PKC-α, c-Myc and LDH-A by α-tocopherol in cancerous mice. α-Tocopherol contributes to the check of cell proliferation by decreasing the activity of LDH-A.
authors: Banaras Hindu University, Varanasi, India.
authors: Renu
authors: R
authors: Sharma
authors: Manjula
authors: M
authors: Vinayak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects* / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D051571:Protein Kinase C-alpha / Q000235:genetics* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D051571:Protein Kinase C-alpha; D024502:alpha-Tocopherol