Abstract
Statins inhibit the synthesis of mevalonate, a precursor isoprenoid molecule to geranylgeraniol that is necessary for the post-translational modification of several small GTPase oncogenes. Despite numerous preclinical studies suggesting that statins can be effective anticancer agents, prospective clinical trials have failed to demonstrate any clinical benefit in patients with cancer. We previously demonstrated that geranylgeraniol suppresses the activity of statins in cell culture studies, and that pitavastatin can cause regression of ovarian cancer xenografts in mice if the animals' diet is modified to avoid the inclusion of geranylgeraniol. Dietary sources of geranylgeraniol may consequently limit the activity of statins in cancer clinical trials. The present study tested several foods to identify those that affected the cytotoxic activity of pitavastatin towards ovarian cancer cells. Solvent extracts of several foods were tested for their ability to suppress the effects of pitavastatin in cell growth assays. The results revealed that pitavastatin induced cell death in ovarian cancer cells (IC(50)=5.2 µM) and this was blocked by geranylgeraniol whereas other products of the mevalonate pathway (coenzyme Q, dolichol or cholesterol) had no effect on the activity of pitavastatin in cell growth assays. Solvent extracts from several foods, especially oils (apart from rapeseed), also blocked the cytotoxic activity of pitavastatin. Several extracts from a range of fruit, vegetables and carbohydrate-rich foods also did not block the activity of pitavastatin. However, extracts from beans, lettuce, oats, eggs and various nuts reduced the activity of pitavastatin. These data identified foods that patients could eat to potentially improve the outcome of clinical trials of pitavastatin in cancer.