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 (IC50=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.