Reactive oxygen species mediate isoalantolactone-induced apoptosis in human prostate cancer cells

Azhar Rasul, Jun Di, Faya Martin Millimouno, Mahadev Malhi, Ichiro Tsuji, Muhammad Ali, Jiang Li, Xiaomeng Li

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Isoalantolactone, a medicinal plant-derived natural compound, is known to induce apoptosis in various cancer cell lines. However, its effect on apoptosis in prostate cancer cells has not been addressed. Thus, we examined the effects of isoalantolactone on prostate cancer cells. It was found that isoalantolactone inhibits growth of both androgen-sensitive (LNCaP) as well as androgen-independent (PC3 and DU-145) prostate cancer cells in a dose-dependent manner. Furthermore, our results indicate that isoalantolactone-induced apoptosis in prostate cancer PC3 cells is associated with the generation of ROS and dissipation of mitochondrial membrane potential (Δψm). In addition, isoalantolactone triggers apoptosis in prostate cancer cells via up-regulation of Bax, down-regulation of Bcl-2, survivin, and significant activation of caspase-3. Isoalantolactone-induced apoptosis is markedly abrogated when the cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, suggesting that the apoptosis-inducing effect of isoalantolactone in prostate cancer cells is mediated by reactive oxygen species. These findings indicate that isoalantolactone induces reactive oxygen species-dependent apoptosis in prostate cancer cells via a novel mechanism involving inhibition of survivin and provide the rationale for further in vivo and preclinical investigation of isoalantolactone against human prostate cancer.

Original languageEnglish
Pages (from-to)9382-9396
Number of pages15
JournalMolecules
Volume18
Issue number8
DOIs
Publication statusPublished - 2013 Aug 1

Keywords

  • Apoptosis
  • Isoalantolactone
  • Prostate cancer
  • Reactive oxygen species

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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