Apoptosis-based drug screening and detection of selective toxicity to cancer cells

Oskar S. Frankfurt, Awtar Krishan

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The goal of our study was to determine whether an apoptosis assay used after short-term drug exposure could predict selective toxicity to cancer cells. To this end we compared the effect of eight anticancer drugs and 10 toxic compounds without known antitumor activity in cultures of human breast cancer cells and normal diploid fibroblasts by Apoptosis ELISA and growth inhibition assays. There was an overlap in concentration values of drugs and toxins inhibiting proliferation in cancer cells. In contrast, Apoptosis ELISA clearly distinguished between the two groups of compounds. Anticancer drugs induced apoptosis in cancer cells at 0.0015-0.5 μM, while toxins were effective at much higher concentrations of 8.0-50.0 μM. Moreover, six out of the 10 toxins did not induce apoptosis in cancer cells. The normal:cancer cell (N:C) ratio for growth inhibiting concentrations was in a similar range for anticancer drugs and toxins. The N:C ratio for apoptosis inducing concentrations was 33-200 for anticancer drugs and 1.3-3.0 for toxins. Our data indicate that apoptosis assays could be used to detect selective toxicity of anticancer drugs by determining apoptosis induction in cancer cells or through a comparison of apoptosis-inducing concentrations in normal and cancer cells.

Original languageEnglish
Pages (from-to)555-561
Number of pages7
JournalAnti-Cancer Drugs
Volume14
Issue number7
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Preclinical Drug Evaluations
Apoptosis
Neoplasms
Pharmaceutical Preparations
Enzyme-Linked Immunosorbent Assay
Poisons
Growth
Drug-Related Side Effects and Adverse Reactions
Diploidy
Fibroblasts
Breast Neoplasms

Keywords

  • Anticancer drugs
  • Apoptosis
  • Drug screening
  • ELISA
  • Selective toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

Cite this

Apoptosis-based drug screening and detection of selective toxicity to cancer cells. / Frankfurt, Oskar S.; Krishan, Awtar.

In: Anti-Cancer Drugs, Vol. 14, No. 7, 01.08.2003, p. 555-561.

Research output: Contribution to journalArticle

Frankfurt, Oskar S. ; Krishan, Awtar. / Apoptosis-based drug screening and detection of selective toxicity to cancer cells. In: Anti-Cancer Drugs. 2003 ; Vol. 14, No. 7. pp. 555-561.
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