Pharmacological ascorbate triggers apoptotic pathway in liver cancer cells via up regulation of TNF-α
By: Muhammad Imran Raza, Abeera Sikandar, Hajra Sadia
Key Words: Hepatocellular Carcinoma, Intravenous vitamin-C, Cancer cell cytotoxicity, TNFα induced apoptosis
Int. J. Biosci. 9(6), 253-258, December 2016.
Ascorbic acid (Vitamin-C) is known to have tumor preventive and anti-tumor effects but the mechanism through which it regulates tumor progression needs to be elucidated. Probably, vitamin-C exerts its cytotoxic effects through TNFα mediated apoptotic pathway. TNFα induces two pathways simultaneously, that are, inflammatory and apoptotic pathways. In tumor cells the balance between apoptotic and inflammatory pathways is disturbed. TNFα induced NF-κB signaling is thought to be responsible for the inflammatory pathway and is implicated in many chronic diseases/disorders including cancer. Inhibition of inflammatory pathway at some point may allow only apoptotic pathway to proceed further, resulting in cancer cell death. This study was designed to evaluate the cytotoxic effect of ascorbic acid on Hepatocellular Carcinoma cells. Cell viability study was accessed after exposing the cells to increasing concentration of vitamin C. Expression of genes involved in signaling like TNFα and NF-κB was quantified. EC50 of Vitamin-C for Huh-7 was found to be 2.17mM. The expression profiling showed that TNFα was elevated, whereas the expression of NF-κB remained unchanged. In synthesis, the study showed that vitamin-C induced TNFα mediate apoptosis by shifting the balance from inflammatory to apoptotic pathway. These findings may be helpful in further understanding of the mechanism of cytotoxicity in cancer cells induced by high dose vitamin-C.