Tanshinones as Effective Therapeutic Agents for Prostate Cancer.

摘要

The purposes of this project were to evaluate if the tanshinone I (T1) and tanshinone IIA (T2A) combinations have synergistic effects on the growth of prostate tumors and to elucidate the cellular and molecular mechanisms of actions. The rationale of proposing synergistic combination of T1 and T2A was based on our preliminary data showing that T1 and T2A had the potent anti-angiogenesis and anti-prostate cancer growth activities, respectively. The results from this research project showed that T1 and T2A alone showed significant effects on inhibiting the growth of androgenindependent PC3 tumors, and that T1 and CT, but not T2A, showed significant effects on inhibiting the growth of androgen-dependent LNCaP tumor. Tanshinones showed minimal side effect on food intake or body weight. On the other hand, the proposed T1 and T2A combination did not show a synergistic or an additive effect, but rather an antagonistic effect on prostate tumor growth in vivo. This unexpected combination effect was supported by the later in vitro studies showing that the T1 and T2A combination indeed had a suggested antagonistic effect on prostate cancer cell growth. The in vitro studies also strongly suggest that the CT and T1 combination, or the CT and T2A combination may have synergistic effect on prostate cancer cell growth. Mechanism studies defined Aurora A (and also possibly Aurora B) and SIRT1 may be important functional molecular targets for tanshinones actions. Our research supports tanshinones, especially T1, as efficacious and safe agents for prostate cancer prevention and therapy, and suggests that tanshinones may be a novel group of candidate agents as Aurora kinases inhibitors. Our research also strongly suggest the rationale to future investigate the synergistic effect of T1 and CT combination regimen for effective prevention and therapy of prostate cancer.