The antiproliferation effects of pipernonaline, a piperine derivative, were investigated on human prostate cancer PC-3 cells.
It inhibited growth of androgen independent PC-3 and androgen dependent LNCaP prostate cells in a dose-dependent (30-90 μM) and time-dependent (24-48 h) manner. The growth inhibition of PC-3 cells was associated with sub-G1 and G0/G1 accumulation, confirmed by the down-regulation of CDK2, CDK4, cyclin D1 and cyclin E, which are correlated with G1 phase of cell cycle. Pipernonaline up-regulated cleavage of procaspase-3/PARP, but did not change expression of proapoptotic bax and antiapoptotic bcl-2 proteins. Its caspase-3 activation was confirmed by the caspase-3 assay kit. In addition, pipernonaline caused the production of reactive oxygen species (ROS), increase of intracellular Ca2+, and mitochondrial membrane depolarization, which these phenomena were reversed by N-acetylcysteine, a ROS scavenger. The results suggest that pipernonaline exhibits apoptotic properties through ROS production, which causes disruption of mitochondrial function and Ca2+ homeostasis and leads to its downstream events including activation of caspase-3 and cleavage of PARP in PC-3 cells. This is the first report of pipernonaline toward the anticancer activity of prostate cancer cells, which provides a role for candidate agent as well as the molecular basis for human prostate cancer.
Written by:
Lee W, Kim KY, Yu SN, Kim SH, Chun SS, Ji JH, Yu HS, Ahn SC. Are you the author?
Department of Urology, Pusan National University Hospital, Busan 602-739, South Korea.
Reference: Biochem Biophys Res Commun. 2013 Jan 4;430(1):406-12.
doi: 10.1016/j.bbrc.2012.11.030
PubMed Abstract
PMID: 23159637
UroToday.com Investigative Urology Section