Cytotoxic activity of Apomine is due to a novel membrane-mediated cytolytic mechanism independent of apoptosis in the A375 human melanoma cell line

Alan Pourpak, Robert T. Dorr, Ross O. Meyers, Marianne B. Powell, Steven P. Stratton

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Apomine, a novel bisphosphonate ester, has demonstrated anticancer activity in a variety of cancer cell lines; however, its mechanism of cytotoxicity is not well understood. Previous work has demonstrated that Apomine induces cell death by activation of caspase-3 in several cancer cell types. However, we have demonstrated that Apomine induces cell death in the A375 human melanoma cell line through a novel membrane-mediated mechanism that is independent of caspase-3 activation. This mechanism of membrane lysis may apply to other bisphosphonates and may be an important mechanism for overcoming resistance to apoptosis. Interestingly, Apomine-mediated cell death in the A375 and UACC 3093 human melanoma cell lines is also independent of N-Ras farnesylation, which was a previously described mechanism of action for Apomine in other cancer cell types. These data suggest that Apomine induces cell death through a novel plasma membrane-mediated cytolytic pathway, independent of caspase-3 activation and N-Ras farnesylation.

Original languageEnglish (US)
Pages (from-to)107-114
Number of pages8
JournalInvestigational New Drugs
Volume25
Issue number2
DOIs
StatePublished - Apr 1 2007

Keywords

  • Apomine
  • Apoptosis
  • Cytolytic
  • Melanoma
  • N-Ras

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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