Cell-based assays for profiling activity and safety properties of cancer drugs

Weiwei Li, Marilyn S. Lam, Andrew Birkeland, Angela Riffel, Leticia Montana, Mark E. Sullivan, Joseph M. Post

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Introduction: Our goal was to establish versatile and high capacity assays to characterize activity and toxicity of chemotherapeutics. The major anti-cancer activity indicators of these agents included inhibition of proliferation and induction of apoptosis to cancer cells. In addition, cytotoxicity and myelosuppressive activity to normal cells were parameters to evaluate toxicity of these drugs. Methods: Using a panel of cell-based assay systems, we investigated activity and toxicity properties of selected cancer drugs. Drug effects on a number of normal and cancer cell types from human origin were evaluated. Results: Topoisomerase inhibitors (camptothecin, doxorubicin and etoposide) and microtubule inhibitors (colchicine and paclitaxel) showed anti-proliferation activity and induced apoptosis in MDA-231 cancer cells. Except for doxorubicin, these drugs had relatively low toxicity to normal cells because the dosage required for cytotoxicity EC50 was > 200-folds higher than the dosage for anti-proliferation EC50 in cancer cells (MDA-231, HL60). However, these drugs were potent inducers of myelotoxicity in human bone marrow progenitor cells. In comparison, the DNA alkylating agents (cisplatin and carboplatin) were less potent proliferation inhibitors (EC50 > 10 μM) in MDA-231 cells and they were also less myelosuppressive. Discussion: Using marketed drugs as examples, our study established a multiple assay platform for profiling in vitro properties of cancer drugs. In drug discovery, such a platform will help to expedite lead selection at early stage.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalJournal of pharmacological and toxicological methods
Volume54
Issue number3
DOIs
StatePublished - Nov 2006
Externally publishedYes

Keywords

  • Anti-proliferation
  • Apoptosis
  • Cancer cell line
  • Cytotoxicity
  • Human primary cells
  • Immunotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint

Dive into the research topics of 'Cell-based assays for profiling activity and safety properties of cancer drugs'. Together they form a unique fingerprint.

Cite this