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 language | English (US) |
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Pages (from-to) | 107-114 |
Number of pages | 8 |
Journal | Investigational New Drugs |
Volume | 25 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- Apomine
- Apoptosis
- Cytolytic
- Melanoma
- N-Ras
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)