Resistance to apoptosis induced by topoisomerase I inhibitors in multidrug-resistant HL60 leukemic cells

Valérie Palissot, Rajae Belhoussine, Yves Carpentier, Stéphane Sebille, Hamid Morjani, Michel Manfait, Jean Dufer*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

The induction of apoptosis by topoisomerase I inhibitors, camptothecin and SN38, was evaluated in drug-sensitive HL60 and multidrug-resistant (MDR) HL60-Vinc leukemic cells. MDR cells displayed a partial resistance to these apoptotic stimuli and this phenomenon was not modulated by verapamil. Basal free calcium concentrations were similar in both cell sublines and were not modified during treatment. Cytoplasmic pH was more acidic in sensitive cells than in MDR cells. Moreover, a significant acidification was obtained during the early stage of apoptosis in sensitive HL60 cells only. Basal Bcl-2 protein expression was found to be greater in MDR than in sensitive cells and was not modulated by apoptosis inducers. This increase of Bcl-2 in MDR cells could be due to the selection process as vincristine enhances Bcl-2 phosphorylation and expression in HL60 sensitive cells. MDR HL60-Vincristine cells therefore display a resistance to apoptosis induced by non-MDR drugs, possibly by Bcl-2 overexpression and inability of these drugs to mediate intracellular pH changes in these drug-resistant cells.

Original languageEnglish
Pages (from-to)918-922
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume245
Issue number3
DOIs
Publication statusPublished - 28 Apr 1998
Externally publishedYes

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