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.

Keywords::

• α-Tocopherol
• lymphoma
• PKC-α
• c-Myc
• LDH-A

Acknowledgements

Research was supported by the Department of Science and Technology, India. Renu Sharma thanks the University Grant Commission, India, for providing a “Research Fellowship in Science for Meritorious Students.”

Potential conflict of interest:

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