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

Wan Lee, Kwang Youn Kim, Sun Nyoung Yu, Sang Hun Kim, Sung Sik Chun, Jae Hoon Ji, Hak Sun Yu, Soon Cheol Ahn

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 (30-90μM) and time-dependent (24-48h) 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.

Original languageEnglish (US)
Pages (from-to)406-412
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume430
Issue number1
DOIs
StatePublished - Jan 4 2013
Externally publishedYes

Keywords

  • Ca flux
  • Cell cycle arrest
  • Mitochondrial membrane potential
  • Pipernonaline
  • Prostate cancer
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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