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The roots and leaves of Angelica keiskei (AK) have been used for the treatment of various diseases including coronary heartdisease, hypertension, and cancer in the Korean folk medicine. However, the mechanism by which methylenechloride fraction (MF) from AK exerts anti-tumorigenic activity in human prostate cancer cells has not been fully understood. In the present study, we report the MF exerted the highest cytotoxicity against prostate cancer DU145 cells compared with other fractions. Especially, MF caused the accumulation of sub-G1 DNA contents of cell cycle and increased annexin V-positive apoptotic bodies and DNA fragmentation. MF down-regulated several proliferative (Cyclin D1) and anti-apoptotic (Bcl-xl, Bcl-2, IAP-1/2, and survivin)gene products in these cells. Hence, MF induced apoptosis through the caspase-3 activation in DU145 cells. We further confirmed that caspase-3 plays an importance role in MF-induced apoptosis in DU145 cells by using caspase-3 inhibitor. Additionally, we observed that MF potentiated Dox-induced apoptosis in DU145 cells. Taken together, our data demonstrate the evidence that MF induces apoptosis depend on caspase-3 activation of and overcomes resistance to chemotherapy in human prostate cancer cells.
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