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INHIBITORY EFFECTS OF EVODIAMINE ON THE CELL GROWTH OF HUMAN PROSTATE CANCER CELL LINE LNCaP .
Kan, Shu-Fen1, Tseng, Yi-Ching1, Yeh, Jiun-Yih1, Wang, Paulus1, 1
ABSTRACT- Evodiamine is one of the major bioactive compounds isolated from Chinese herbal drug named Wu-Chu-Yu. According to previous reports, Wu-Chu-Yu exerts an antiproliferation effect on several cancers including breast, lung, and kidney cancers. Prostate carcinoma is one of the most common malignant tumors and the second leading cause of cancer death in male in United States. Furthermore, it becomes a more and more common cancer among men in Asia during past ten years. In the present study, we examined whether evodiamine exhibited the inhibitory effects on the growth of androgen-dependent prostate cancer cell line LNCaP in vitro. Evodiamine significantly inhibited the growth of LNCaP cells in a dose- and time-dependent manner, measured by mitochondrial reduction of MTT [3-(4,5-dimethylthiazol-2-yle)2,5-diphenyltetrazolium bromide]. Incubation of R1881 (an androgen receptor activator, 0.01 nM) increased the growth of LNCaP cells. The increased cell growth induced by R1881 were dose-dependently inhibited by administration of evodiamine (0.1~100 M). To observe the cell cycle progression, cells were treated with or without various doses of evodiamine (1~100 M), and quantified by propidium iodide staining and flow cytomestry analysis. The results of flow cytometry indicated that administration of evodiamine caused an accumulation of LNCaP cells in G2/M phase and increased the hypodiploid cells. These data suggest that evodiamine inhibits the growth of prostate cancer cell line, LNCaP, through an accumulation of cell cycle in G2/M phase and induces cell death. The expression and activity of androgen receptor might play an important role involved in evodiamine-induced cell death and cell cycle arrest in LNCaP cells. We expect that the results will provide a new strategy for prevention or therapy of prostate carcinoma in human beings.
KEY WORDS: Evodiamine, Prostate, Cell cycle, Androgen
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