title: Pipernonaline from Piper longum Linn. induces ROS-mediated apoptosis in human prostate cancer PC-3 cells.
abstract: 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.
authors.affiliation: Department of Urology, Pusan National University Hospital, Busan 602-739, South Korea.
authors.forename: Wan
authors.initials: W
authors.lastname: Lee
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.forename: Sun-Nyoung
authors.initials: SN
authors.lastname: Yu
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung-Sik
authors.initials: SS
authors.lastname: Chun
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Ji
authors.forename: Hak-Sun
authors.initials: HS
authors.lastname: Yu
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D031701:Piper / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C419151:pipernonaline; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3