Abstract
Prostate cancer is the second‐leading cause of cancer death in American men. Current therapeutic approaches have made significant progression in the control of prostate cancer progression. On the other hand, conventional therapeutics have variable efficacies and are usually associated with metastatic recurrence and/or high cytotoxicity. Therefore the search for effective chemopreventive agents with minimal side effects has remained one of the top priorities in prostate cancer research. Some Chinese herbal medicines have been used for centuries, thus certain Chinese medicines with active anti‐cancer ingredients may be effective candidates for the prevention and/or treatment of prostate cancer. Danshen (Salvia miltiorrhiza) has been widely adopted in the traditional Chinese medicinal preparations for treatment of cerebrovascular disorders with minimal side effects. We thus evaluated the effects of several major Danshen components, tanshinones IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT) on the growth of prostate cancer cells and identified the potential molecular targets that were responsive to and might be responsible for the treatments. CT, T2A and T1 significantly inhibited the growth of prostate cancer cells with the IC50s at a few Ms associated with cell cycle arrests and apoptosis induction in vitro, whereas their growth inhibition effects on normal prostate epithelial cells were dramatically reduced by 5–10 folds. T1 showed the most potent activity among the three compounds, but the combination of CT and T2A showed synergistic effects against prostate cancer cell growth. The pilot animal study verified that T1 inhibited the growth of DU145 tumors in a dose‐dependent manner. By using the real time PCR arrays for epigenetic markers, we identified Aurora A kinase gene as a potential molecular target of tanshinones. Aurora A gene and protein were up‐regulated in prostate cancer cell lines when compared with that in the normal cells, and the tanshinone treatments significantly down‐regulated its expression. These results demonstrated potent anti‐prostate cancer activities of tanshinones and identified Aurora A as a potential molecular target of tanshinones actions. Further in vivo studies of the chemopreventive effects of tanshinones and the CT and T2A combination on prostate cancer development and/or progression are warranted.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A75.
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