Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3.
Prostate carcinoma is one of the most common malignant tumors and has become a more common cancer in men. Previous studies demonstrated that evodiamine (EVO) exhibited anti-tumor activities on several cancers, but its effects on androgen-independent prostate cancer are unclear. In the present study, the action mechanisms of EVO on the growth of androgen-independent prostate cancer cells (DU145 and PC3 cells) were explored. EVO dramatically inhibited the growth and elevated cytotoxicity of DU145 and PC3 cells. The flow cytometric analysis of EVO-treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest was accompanied by elevated Cdc2 kinase activity, an increase in expression of cyclin B1 and phosphorylated Cdc2 (Thr 161), and a decrease in expression of phosphorylated Cdc2 (Tyr 15), Myt-1, and interphase Cdc25C. TUNEL examination showed that EVO-induced apoptosis was observed at 72 h. EVO elevated the activities of caspase 3, 8, and 9 in DU145 cells, while in PC3 cells only the activities of caspase 3 and 9 were elevated. EVO also triggered the processing of caspase 3 and 9 in both DU145 and PC3 cells. We demonstrate that roscovitine treatment result in the reversion of G2/M arrest in response to EVO in both DU145 and PC3. However, inhibitory effect of roscovitine on EVO-induced apoptosis could only be observed in DU145 rather than PC3. In DU145, G2/M arrest might be a signal for initiation of EVO-triggered apoptosis. Whereas EVO-triggered PC3 apoptosis might be independent of G2/M arrest. These results suggested that EVO inhibited the growth of prostate cancer cell lines, DU145 and PC3, through an accumulation at G2/M phase and an induction of apoptosis.
Kan
Shu-Fen
SF
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
Yu
Ching-Han
CH
Pu
Hsiao-Fung
HF
Hsu
Jong-Ming
JM
Chen
Ming-Jen
MJ
Wang
Paulus S
PS
D000728:Androgens / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002277:Carcinoma / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000473:pathology; D011687:Purines / Q000494:pharmacology; D011799:Quinazolines / Q000633:toxicity*; D000077546:Roscovitine
D000728:Androgens; C534699:CCNB1 protein, human; D003470:Culture Media; D019926:Cyclin B; D056744:Cyclin B1; D004273:DNA, Neoplasm; D010936:Plant Extracts; D011687:Purines; D011799:Quinazolines; D000077546:Roscovitine; C049639:evodiamine; D007770:L-Lactate Dehydrogenase; D016203:CDC2 Protein Kinase; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9