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ATPase inhibitors suppress actinomycin D-induced apoptosis in leukemia cells

Yoshihito Shiono1, Yasuko Fujita, Syuichi Oka

  • 1Research Institute of Biological Resources, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.

Anticancer Research
|January 18, 2003
PubMed
Abstract

Insights

Eight ATPase inhibitors were tested for their effect on apoptosis. Geldanamycin and radicicol, specific inhibitors of Heat Shock Protein 90 (HSP90) ATPase, significantly suppressed apoptosis, indicating HSP90 ATPase activity is involved in programmed cell death.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Apoptosis, or programmed cell death, is a crucial biological process regulated by various enzymes.
  • While caspases, DNases, and protein kinases are known players, the role of ATPases in apoptosis remains incompletely understood.

Purpose of the Study:

  • To investigate the involvement of ATPase activity in the process of apoptosis.
  • To determine the specific effects of various ATPase inhibitors on apoptosis induction in a human leukemia cell line.

Main Methods:

  • Utilized human megakaryoblastic leukemia CMK-7 cells induced into apoptosis using actinomycin D and colcemid.
  • Assessed the impact of eight distinct ATPase inhibitors on key apoptosis markers: caspase-3 activation and DNA cleavage.
  • Employed Western blotting to analyze the cleavage of procaspase-9.

Main Results:

  • Five of the tested ATPase inhibitors, including 2,3-Butanedione monoxime (BDM), lansoprazole, cyclopiazonic acid, geldanamycin, and radicicol, demonstrated a suppressive effect on apoptosis.
  • Geldanamycin exhibited the most potent inhibition of both caspase-3 activation and DNA cleavage.
  • Radicicol showed a stronger suppression of procaspase-9 cleavage compared to BDM, lansoprazole, and cyclopiazonic acid.

Conclusions:

  • The findings suggest that ATPase activity, particularly within Heat Shock Protein 90 (HSP90), plays a significant role in regulating apoptosis.
  • Geldanamycin and radicicol, as specific HSP90 ATPase inhibitors, provide strong evidence for HSP90's involvement in the apoptotic pathway.

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