Cyclosporin A potentiates the cytotoxic effects of methyl methanesulphonate in HL-60 and K562 cells
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Apoptosis drug effects MeSH
- K562 Cells drug effects enzymology pathology MeSH
- Cyclosporine toxicity MeSH
- DNA, Neoplasm drug effects MeSH
- Glutathione metabolism MeSH
- Glutathione Disulfide metabolism MeSH
- HL-60 Cells drug effects enzymology pathology MeSH
- Immunosuppressive Agents toxicity MeSH
- Caspase 3 biosynthesis MeSH
- Humans MeSH
- RNA, Messenger metabolism MeSH
- Methyl Methanesulfonate toxicity MeSH
- Necrosis chemically induced MeSH
- Oxidative Stress drug effects MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics metabolism MeSH
- DNA Damage MeSH
- RNA, Neoplasm analysis MeSH
- Drug Synergism MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclosporine MeSH
- DNA, Neoplasm MeSH
- Glutathione MeSH
- Glutathione Disulfide MeSH
- Immunosuppressive Agents MeSH
- Caspase 3 MeSH
- RNA, Messenger MeSH
- Methyl Methanesulfonate MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- RNA, Neoplasm MeSH
Methyl methanesulphonate (MMS) is a DNA damaging agent, which induces oxidative stress, ATP depletion, and consequently, cell death, in HL-60 and K562 cells. The cell death induced by MMS predominantly exhibited the morphological and biochemical hallmarks of necrosis. A minor population of dying cells exhibited apoptotic hallmarks, especially in K562 cell cultures. Cyclosporin A (CsA) was used to modulate the MMS-induced cell death. Our results indicated that CsA did not prevent cells from dying, but changed the mode of death from necrotic to apoptotic. Surprisingly, CsA enhanced oxidative stress and increased the overall number of dead cells. Based on these results, we conclude that the modulatory effect of CsA on MMS-induced cell death might arise from an interference by CsA with mitochondrial metabolism, rather than from inhibition of the MMS efflux mediated by P-glycoprotein.
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