Loss of PTEN Facilitates Rosiglitazone-Mediated Enhancement of Platinum(IV) Complex LA-12-Induced Apoptosis in Colon Cancer Cells.
We demonstrated for the first time an outstanding ability of rosiglitazone to mediate a profound enhancement of LA-12-induced apoptosis associated with activation of mitochondrial pathway in human colon cancer cells. This effect was preferentially observed in the G1 cell cycle phase, independent on p53 and PPARγ proteins, and accompanied with significant changes of selected Bcl-2 family protein levels. Further stimulation of cooperative synergic cytotoxic action of rosiglitazone and LA-12 was demonstrated in the cells deficient for PTEN, where mitochondrial apoptotic pathway was more stimulated and G1-phase-associated dying was reinforced. Our results suggest that combined treatment with rosiglitazone and LA-12 might be promising anticancer strategy in colon-derived tumours regardless of their p53 status, and also favourable in those defective in PTEN function.
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic; Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Jarmila
J
Lauková
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic; Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Alois
A
Kozubík
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic; Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Jiřina
J
Hofmanová
Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Jana
J
Nekvindová
Platinum Pharmaceuticals, a.s., Brno, Czech Republic.
Petr
P
Sova
INCELL Corporation LLC, San Antonio, Texas, United States of America.
Mary Pat
MP
Moyer
Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Jiří
J
Ehrmann
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.
Alena
A
Hyršlová Vaculová
D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D047495:PPAR gamma; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53; C482801:bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV); D000077154:Rosiglitazone; D000547:Amantadine; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse