New research has opened up the prospect that gossypol – a drug refined from cottonseed oil and previously tried and abandoned as a male contraceptive – could boost the effectiveness of treatment for prostate tumours and possibly other common cancers as well.
Dr. Liang Xu, a research assistant professor at the University of Michigan, reported today (Friday 1 October) to the EORTC-NCI-AACR[1] Symposium on Molecular Targets and Cancer Therapeutics in Geneva that gossypol has been shown by many groups to have anti-tumour activities.
But his team, under the leadership of Dr Marc Lippman and Dr Shaomeng Wang at the University’s Comprehensive Cancer Center, has now demonstrated that a potential small molecule inhibitor of Bcl-2/xL proteins can boost the efficacy of radiotherapy and chemotherapy. They showed that the molecule, (-)-gossypol (minus gossypol)[2], inhibited the anti-apoptotic function of Bcl-2/xL in cells, and increased induction of apoptosis (programmed cell death) and made the tumours more sensitive to radiotherapy in human prostate tumours in mice. The study demonstrates for the first time that(-)-gossypol enhances the anti-tumour efficacy of radiation therapy both in vitro and in vivo with increased induction of apoptosis.
Dr. Xu explained: "The significance of this is that Bcl-2 and Bcl-xL proteins are over expressed in many cancers, making them resistant to drug and radiation treatment. So, it is not just prostate cancer that our findings are relevant to, but also other cancers with BcL-2/xL expression, such as those of the lung, breast, ovary, pancreas, skin, brain and head and neck, where (-)-gossypol may also sensitise cancer cells to chemo/radiotherapy."
He said that based on their cell and animal data the (-)-gossypol form of the drug was likely to be more active than the same doses of natural gossypol used in previous studies. Furthermore, their cell and animal data show that (-)-gossypol would make radiotherapy and chemotherapy more powerful and overcome the resistance to drug and radiation treatment caused by high levels of Bcl-2/xL.