TY - JOUR
T1 - Resistance to apoptosis induced by topoisomerase I inhibitors in multidrug-resistant HL60 leukemic cells
AU - Palissot, Valérie
AU - Belhoussine, Rajae
AU - Carpentier, Yves
AU - Sebille, Stéphane
AU - Morjani, Hamid
AU - Manfait, Michel
AU - Dufer, Jean
N1 - Funding Information:
We thank G. Laurent and J. P. Jaffrezou for HL60-Vinc cells and F. Belloc for his help in ¯ow cytometry. This work was supported by grants from the Comite DeÂpartemental des Ardennes de la Ligue contre le Cancer and from RhoÃne-Poulenc-Rorer. V.P. is allocataire-moniteur from the French Ministry of Research and Universities.
PY - 1998/4/28
Y1 - 1998/4/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032576982&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/9588215
U2 - 10.1006/bbrc.1998.8550
DO - 10.1006/bbrc.1998.8550
M3 - Article
C2 - 9588215
AN - SCOPUS:0032576982
SN - 0006-291X
VL - 245
SP - 918
EP - 922
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -