The genotoxic effects of anti-cancer drug gossypol on human lymphocytes and its mitigation by melatonin

Purpose of study: To determine melatonin as a potential natural antioxidant to mitigate the genotoxic effects of promising anti-cancer drug gossypol in human lymphocytes. Introduction: Gossypol, is a polyphenolic compound naturally occurring in cotton seed, was originally identified as a male contraceptive but it has several proposed clinical applications. Gossypol has anti-proliferative effects on cancer cell lines. However, its genotoxic effects on normal cells are not much studied. Hence, there is a paucity of data available. Hence, the study was conducted to investigate gossypol-induced genotoxic effects on lymphocytes. Methods: Peripheral blood lymphocyte cultures (PBLC) were done and exposed by two different doses of an anti-cancer drug, gossypol (0.274mM, 1.645mM) to check genotoxic effects. Melatonin (0.2mM) is used as an antioxidant. Genotoxic indices such as sister chromatid exchanges (SCEs), cell cycle proliferative index (CCPI), average generation time (AGT), population doubling time (PDT) were assayed in the cultures. Result: Gossypol-treated groups indicated significant increases in frequency of SCEs calculated for SCE/plate and SCE/chromosome. Furthermore, CCPI showed a remarkable reduction and increased AGT and PDT levels were found in exposed cultures. When the higher dose of gossypol cultures was treated along with melatonin, these indices were found to be declined and comparable to control. Conclusion: Gossypol, an anti-cancer drug, induces genotoxicity on lymphocyte cells and co-supplementation of melatonin antioxidant ameliorates these toxic effects of gossypol.