Cytotoxic activity of Apomine is due to a novel membrane-mediated cytolytic mechanism independent of apoptosis in the A375 human melanoma cell line.
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| 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.
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| Authors | Alan Pourpak, Robert T Dorr, Ross O Meyers, Marianne B Powell, Steven P Stratton |
| Journal | Investigational new drugs (Invest New Drugs) Vol. 25 Issue 2 Pg. 107-14 (Apr 2007) ISSN: 0167-6997 [Print] United States |
| PMID | 17024575 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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