Cyclosporin A enhances the apoptotic effects of N-(4-hydroxyphenyl)retinamide in breast cancer cells.
4HPR, an analogue of ATRA, effectively induces growth inhibition and apoptosis in breast cancer cell lines and animal models but is ineffective against advanced human breast tumors. Different compounds, including tamoxifen, are currently being tested to increase 4HPR efficacy in the clinic. Here, we report that cyclosporin A selectively increases the ability of 4HPR, but not ATRA, to induce growth inhibition and apoptosis in ER(+) and ER(-) breast cancer cell lines. Increased apoptosis by the 4HPR and cyclosporin A combination was correlated with increased production of the free radical nitric oxide. Thus, the 4HPR and cyclosporin A combination may potentially be a novel therapeutic modality against breast tumors.
Lim
Soo-Jeong
SJ
Section of Immunobiology and Drug Carriers, Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Simeone
Ann-Marie
AM
Kim
Chong-Kook
CK
Tari
Ana M
AM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011960:Receptors, Estrogen; D017313:Fenretinide; D009569:Nitric Oxide; D014212:Tretinoin; D016572:Cyclosporine