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...

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Bibliographic Details
Published in:PloS one 2015-10, Vol.10 (10), p.e0141020-e0141020
Main Authors: Lauková, Jarmila, Kozubík, Alois, Hofmanová, Jiřina, Nekvindová, Jana, Sova, Petr, Moyer, Mary Pat, Ehrmann, Jiří, Hyršlová Vaculová, Alena
Format: Article
Language:English
Subjects:
Amantadine - analogs & derivatives
Amantadine - pharmacology
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Bcl-2 protein
Biology
Biophysics
Cancer
Cancer cells
Cancer therapies
Cell cycle
Cell Cycle - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Colon
Colon cancer
Colonic Neoplasms - drug therapy
Colorectal cancer
Combined treatment
Cytotoxicity
Drug Synergism
Drugs
Energy Metabolism - drug effects
G1 Phase Cell Cycle Checkpoints - drug effects
HCT116 Cells
Humans
Immunology
Kinases
Ligands
Membrane Potential, Mitochondrial - drug effects
Mitochondria
Mitochondria - metabolism
Organoplatinum Compounds - pharmacology
Ovarian cancer
p53 Protein
Physiology
Platinum
PPAR gamma - genetics
Prostate
Proteins
PTEN Phosphohydrolase - genetics
PTEN protein
RNA Interference
RNA, Small Interfering
Rosiglitazone
Science
Thiazolidinediones
Thiazolidinediones - pharmacology
Tumor proteins
Tumor Suppressor Protein p53 - genetics
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0141020