Different DNA lesions trigger distinct cell death responses in HCT116 colon carcinoma cells

Shaochun Bai, David W. Goodrich

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The pleiotrophic cellular response to DNA damage includes activation of cell cycle checkpoints, induction of DNA repair pathways, and initiation of programmed cell death among others. The fate of cells with damaged DNA depends on the coordination of these different responses. The clinical efficacy of genotoxic therapies is influenced by cell fate and thus by how the DNA damage response is coordinated. While a great deal has been learned about how different DNA lesions activate distinct cell cycle check-points and DNA repair pathways, less is known about whether the type of DNA lesion influences the qualitative and quantitative nature of the cell death response. To address this question, HCT116 colon carcinoma cells have been treated with equally cytotoxic doses of the antitumor DNA alkylating agents adozelesin or bizelesin or the DNA strand scission agent C-1027. The relative contribution of cell cycle arrest and cell death to measured cytotoxicity varied among the three drugs. Apoptotic cell death accounts for most C-1027 cytotoxicity while cell cycle arrest and cell death both contribute to the cytotoxicity of the alkylating agents. Each of the drugs induces a distinct but overlapping pattern of caspase activation. In addition, the cell death response to these drugs is differentially dependent on p53 and p21. These observations suggest that the type of DNA lesion influences not only the relative extent of apoptotic cell death at a given cytotoxic dose but also the qualitative nature of that response.

Original languageEnglish (US)
Pages (from-to)613-619
Number of pages7
JournalMolecular Cancer Therapeutics
Volume3
Issue number5
StatePublished - May 2004
Externally publishedYes

Fingerprint

Colon
Cell Death
Carcinoma
DNA
Cell Cycle Checkpoints
Alkylating Agents
DNA Repair
DNA Damage
Pharmaceutical Preparations
Caspases
Cell Cycle
C 1027

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Different DNA lesions trigger distinct cell death responses in HCT116 colon carcinoma cells. / Bai, Shaochun; Goodrich, David W.

In: Molecular Cancer Therapeutics, Vol. 3, No. 5, 05.2004, p. 613-619.

Research output: Contribution to journalArticle

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