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Pipernonaline from Piper longum Linn. induces ROS-mediated apoptosis in human prostate cancer PC-3 cells.

Lee, W; Kim, KY; Yu, SN; Kim, SH; Chun, SS; Ji, JH; Yu, HS; Ahn, SC
Biochemical and biophysical research communications, 430(1):406-412, 2013
Journal Title
Biochemical and biophysical research communications
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-G(1) and G(0)/G(1) accumulation, confirmed by the down-regulation of CDK2, CDK4, cyclin D1 and cyclin E, which are correlated with G(1) 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 Ca(2+), 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 Ca(2+) 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.
MeSH terms
Alkaloids/chemistry/*pharmacologyAntineoplastic Agents/chemistry/*pharmacologyApoptosis/*drug effectsCaspase 3/metabolismCell Line, TumorCell Proliferation/drug effectsG0 Phase/drug effectsG1 Phase Cell Cycle Checkpoints/drug effectsHumansMalePiper/*chemistryPiperidines/chemistry/*pharmacologyPoly(ADP-ribose) Polymerases/metabolismProstatic Neoplasms/*metabolism/pathologyProto-Oncogene Proteins c-bcl-2/metabolismReactive Oxygen Species/*metabolism
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Journal Papers > Research Organization > Genomic Instability Research Center
AJOU Authors
지, 재훈
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