Flavonoids occurring in many edible fruits and vegetables, typified by fisetin and quercetin, have been suggested to prevent malignancies, including those of the prostate. Only a handful of flavonoids have thus far been subjected to exhaustive pharmacological investigation, and it is unknown whether analogues exist with pharmacological properties superior to those of flavonoids studied to date. We identified TMFol as a potent inhibitor of growth of TRAMP C2, LNCaP, and PC-3 prostate cancer cells, with IC50 values of 1.3-5µM. For comparison, the respective IC50 values for fisetin and quercetin are 8-10 fold higher. Studies in mice hint at the possibility that TMFol may be useful as prostate cancer chemopreventive agent, because TMFol levels in prostate tissue after single oral administration of 240 mg/kg reached 18 nmol/g, and steady state levels after dietary intake (0.2%) were 5 nmol/g These concentrations are consistent with those eliciting growth inhibition in prostate cells in vitro. Mechanistic studies have shown TMFol to arrest cells in the G2M phase of the cell cycle and induce apoptosis. In addition, TMFol inhibited androgen receptor signalling. When nude mice bearing the TRAMP C2 cell xenograft were exposed to TMFol (0.2% in the diet) tumor volume at termination of the experiment was significantly reduced by 41% in comparison to control (p<0.001). Quercetin and fisetin had no effect, at equimolar doses, in the same mouse model. Compared to other flavonoids thus far tested as putative prostate cancer chemopreventive agents, TMFol seems superior in terms of growth-inhibitory potency, and in vivo efficacy, probably related to its metabolic stability. It therefore warrants further preclinical and clinical investigation.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):A104.