Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction

Azhar Rasul, Rui Bao, Mahadev Malhi, Bing Zhao, Ichiro Tsuji, Jiang Li, Xiaomeng Li

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability and apoptosis in human bladder cancer T24 cells. Treatment of T24 cells with costunolide resulted in a dose-dependent inhibition of cell viability and induction of apoptosis which was associated with the generation of ROS and disruption of mitochondrial membrane potential (Δψm). These effects were significantly blocked when the cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP. These findings provide the rationale for further in vivo and clinical investigation of costunolide against human bladder cancer.

Original languageEnglish
Pages (from-to)1418-1433
Number of pages16
JournalMolecules
Volume18
Issue number2
DOIs
Publication statusPublished - 2013 Feb

Keywords

  • Apoptosis
  • Bladder cancer
  • Costunolide
  • Reactive oxygen species
  • T24 cells

ASJC Scopus subject areas

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

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