• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1154-1160
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• 2009

Androgen receptors (AR) play a crucial role in the development and progression of prostate cancer. Many studies have suggested that prostate cancer cell proliferation is inhibited by AR downregulation, and it has been reported that Takrisodokyeum (TRSDY) induced apoptotic cell death and suppressed tumorigenesis in human leukemia cells. Therefore, this study was conducted to elucidate the mechanism by which TRSDY affects cell growth and AR expression in androgen-dependent prostate cancer cells (LNCaP cells). We investigated the proliferation and apoptosis of LNCaP cells using MTT and DNA fragmentation assays. In addition, we used western blot analysis to assess the effects of TRSDY on the expression of the AR target gene, prostate-specific antigen (PSA). Furthermore, the mechanism of AR downregulation by TRSDY was investigated using EMSA to analyze the binding activity of AR to androgen response elements (ARE). TRSDY significantly suppressed proliferation and induced apoptosis in LNCaP cells. In addition, TRSDY-induced apoptotic cell death was accompanied by activation of caspase-3 and cleavage of its substrate, poly(ADP-ribose) polymerase. TRSDY also inhibited the constitutively expressed- or 5a-dihydrotestosterone (DHT)-induced AR/PSA protein levels. However, these effects were mediated by inhibition of the binding of AR to ARE. TRSDY-mediated AR/PSA downregulation contributes to the inhibition of cell proliferation and the induction of apoptosis in LNCaP human prostate cancer cells. Our findings suggest that TRSDY may be used as a chemopreventive or chemotherapeutic agent for the treatment of prostate cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.861-865
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• 2006

Takrisodokyeum (TRSDY) has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in androgen-independent prostate cancer DU145 cells as evidenced by DNA fragmentation and chromatine condensation in hoechst 33342 dye staining. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by increases of PTEN and Par-4 in a time-dependent manner Taken together, these results suggest that TRSDY induce PTEN and Par-4 expression, and eventually lead to apoptotic cell death in androgen independent prostate cancer DU145 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.946-950
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• 2006

Takrisodokyeum (TRSDY) has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in androgen-independent prostate cancer PC-3 cells as evidenced by DNA fragmentation. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by decreases of PAKT and $NF-{\kappa}$ activation, which is resulted from inhibition of $I{\kappa}B-{\alpha}$ degradation. But TRSDY-induced apoptotic effect of PC-3 cells was independent of Par-4 expression. Taken together, these results suggest that TRSDY inhibits AKT phosphorylation and $NF-{\kappa}B$ activation, and eventually leads to apoptotic cell death in androgen independent prostate cancer PC-3 cells.