Evodiamine, isolated from a Chinese herbal
drug named
Wu-Chu-Yu, possesses many
biological functions. Recently, it has been reported that
Wu-Chu-Yu exerts an antiproliferative effect on several
cancers. Prostate
carcinoma initially occurs as an
androgen-dependent
tumor and is the second leading cause of
cancer death in American males. In the present study, the effect of
evodiamine on the growth of
androgen-dependent
prostate cancer cell line LNCaP in vitro was examined. Based on [3-(4,5-dimethylthiazol-2-yle)2,5-diphenyltetrazolium
bromide] (MTT) assay,
evodiamine significantly inhibited the growth of LNCaP cells in a concentration-dependent manner. A significant and concentration-dependent inhibitory effect of
evodiamine on LNCaP cell growth was observed at 24 hr and persisted for 96 hr. The examination of
lactate dehydrogenase (LDH) assay showed that the cytotoxic effects of
evodiamine on LNCaP cells were concentration dependent. Furthermore, we examined the influences of
evodiamine on cell death and cell cycle. The flow cytometric analysis of
evodiamine-treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest reached a maximum at 24 hr after
evodiamine treatment. The G2/M arrest was accompanied by an elevated p34(cdc2)
kinase activity and an increase in the
protein expression of
cyclin B1 and phosphorylated form of p34(cdc2) (Thr 161). Examination of TUNEL showed that
evodiamine-induced apoptosis was observed at 24 hr and extended for 72 hr.
Evodiamine elevated
caspase-3, and
caspase-9 activities and the processing of
caspase-3 and
caspase-9. These results suggested that
evodiamine inhibits the growth of
prostate cancer cell line, LNCaP, through an accumulation of cell cycle at G2/M phase and an induction of apoptosis.