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Published on: June 29, 2011

Anticancer drug-induced apoptosis in human monocytic leukemic cell line U937 requires activation of endonuclease(s)

P Shrivastava1, A Sodhi, P Ranjan

  • 1School of Biotechnology, Banaras Hindu University, Varanasi, India.

Anti-Cancer Drugs
|April 11, 2000
PubMed

Insights

Anticancer drugs induce apoptosis, a programmed cell death, by triggering DNA fragmentation. Inhibiting this DNA fragmentation prevents cancer cell death, but apoptosis can still occur without it in response to other stimuli.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Apoptosis, or programmed cell death, is crucial for tumor cell elimination by anticancer agents.
  • Endonuclease-mediated internucleosomal DNA fragmentation is a widely recognized marker of apoptosis.
  • The role of DNA fragmentation in drug-induced apoptosis requires further elucidation.

Purpose of the Study:

  • To investigate the role of endonuclease-mediated DNA fragmentation in apoptosis induced by anticancer drugs.
  • To determine if DNA fragmentation is essential for anticancer drug-induced cell death.
  • To explore alternative pathways of apoptosis in the absence of DNA fragmentation.

Main Methods:

  • Induction of apoptosis in human monocytic leukemic cell line U937 using anticancer drugs (adriamycin, etoposide, cisplatin).
  • Inhibition of endonuclease activity using aurintricarboxylic acid and zinc ions.
  • Assessment of DNA fragmentation, morphological changes, nuclear alterations, and cell viability.

Main Results:

  • Anticancer drugs commonly induced endonuclease activation and oligonucleosomal DNA fragmentation.
  • Inhibition of endonuclease activity prevented apoptotic cell death, confirming DNA fragmentation's role.
  • Heat shock induced apoptosis with morphological features of cell death but without significant DNA fragmentation.

Conclusions:

  • Endonuclease-mediated DNA fragmentation is a common and essential event in apoptosis induced by anticancer drugs.
  • While DNA fragmentation is critical for drug-induced apoptosis, alternative apoptotic pathways exist, as demonstrated by heat shock induction.

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