EM012, a microtubule-interfering agent, inhibits the progression of multidrug-resistant human ovarian cancer both in cultured cells and in athymic nude mice

Jun Zhou, Min Liu, Roopa Luthra, Jeremy Jones, Ritu Aneja, Ramesh Chandra, Rajeshwar R. Tekmal, Harish C. Joshi

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Drug resistance, in particular multidrug resistance, is a serious problem that impedes the effectiveness of chemotherapy. Multidrug resistance results mainly from an enhanced efflux of drugs by drug pumps located on the cell membrane such as P-glycoprotein. In the study reported here we showed that EM012, a microtubule-interfering agent, is a weak substrate for P-glycoprotein and inhibited the proliferation of A2780/ADR human ovarian cancer cells, which possess multidrug resistance due to P-glycoprotein overexpression. A2780/ADR cells treated with EM012 exhibited pronounced mitotic arrest, developed large multilobed nuclei, and eventually died through the initiation of apoptosis. Intraperitoneal treatment of A2780/ADR xenograft tumors in athymic nude mice with EM012 significantly inhibited tumor progression through triggering apoptosis and conferred an apparent survival advantage. Furthermore, EM012 treatment did not cause detectable toxicity to normal tissues. These findings suggest that EM012 may serve as a novel chemotherapeutic agent for the treatment of multidrug-resistant human ovarian cancer.

Original languageEnglish (US)
Pages (from-to)461-465
Number of pages5
JournalCancer chemotherapy and pharmacology
Volume55
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Cell cycle
  • EM012
  • Multidrug resistance
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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