The potential roles of gossypol as anticancer agent: advances and future directions

Gossypol is a polyphenol compound found in cotton plants (Gossypium sp.) It is a seed pigment with a protective role. It is also known as an oral male contraceptive for treating gynaecological disorders. Numerous studies have shown its anti-tumour, antioxidant, antiviral, antimicrobial, and immunomodulatory activities  Nevertheless, gossypol has limited application in medicine as a potential pharmacological agent, mainly due to the narrow therapeutic range of doses, the risk of permanent irreversible sterility and hypokalaemia. This problem led to numerous studies aimed at reducing the side effects and toxicity of gossypol and identifying and developing new derivative molecules with reduced side effects and toxicity. The mechanism of anticancer activity of gossypol is the induction of apoptosis through the suppression of anti-apoptotic proteins of the Bcl-2 family . Anticancer activity of gossypol is proven on several different cancer cell lines : human breast cancer cells (MCF-7, MDA-MB-231, MDA-MB-468, ZR-75-1, and T47D), pancreatic cancer cells (BxPC-3 and MIA PaCa-2), human colon cancer cells (COLO 225), human cervical cancer cells (HeLa and SiHa cell lines), non-small cell lung cancer (NSCLC) cell lines (H1975), human lung cancer cell lines (H1299 and H358) and prostate cancer cells. Except in China, where gossypol is available on the drug market as an adjuvant used for tumour treatment [85], in the rest of the world, gossypol is still under clinical trials investigation