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Costunolide induces apoptosis through nuclear calcium2+ overload and DNA damage response in human prostate cancer

Jui-Ling Hsu1, Shiow-Lin Pan, Yunn-Fang Ho

  • 1School of Pharmacy, National Taiwan University, Taipei, Taiwan, Republic of China.

The Journal of Urology
|March 23, 2011
PubMed
Abstract

Insights

Costunolide effectively combats prostate cancer cells by depleting thiols and overloading calcium, triggering cell cycle arrest and apoptosis. This natural compound shows promise for chemotherapy, especially in androgen-refractory cases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Costunolide is a natural sesquiterpene lactone.
  • Prostate cancer, particularly androgen-refractory prostate cancer, remains a significant therapeutic challenge.

Purpose of the Study:

  • To elucidate a novel mechanism of costunolide action in prostate cancer.
  • To highlight costunolide's potential as a chemotherapy agent for prostate cancer.

Main Methods:

  • Pharmacological and biochemical assays were employed.
  • Apoptotic signaling pathways in prostate cancer cells were characterized.
  • Cellular effects were assessed using sulforhodamine B assay, clonogenic test, and flow cytometry.

Main Results:

  • Costunolide demonstrated antiproliferative activity against hormone-dependent and independent prostate cancer cells.
  • It induced nuclear calcium overload, DNA damage, and ATR phosphorylation in PC-3 cells.
  • Costunolide caused G1-phase cell cycle arrest via p21/CDK2/cyclin E/Rb pathway modulation.
  • Effects were linked to intracellular thiol depletion and calcium mobilization, not reactive oxygen species.

Conclusions:

  • Costunolide induces intracellular thiol depletion and nuclear calcium overload, leading to DNA damage and p21 up-regulation.
  • This mechanism results in cell cycle arrest at G1 phase and subsequent apoptosis in prostate cancer cells.
  • Costunolide presents a promising therapeutic strategy for prostate cancer treatment.

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