ABSTRACT
The effect of curcumin on the resistance of SKOV-3 human ovarian adenocarcinoma cells to cisplatin was studied. It was found that curcumin induced "reversal" of cancer cells resistance, which was associated with suppression of the expression of genes encoding the key antioxidant enzymes (SOD1, SOD2, CAT, GPX1, and HO-1) and transcription factor Nrf2 and a decrease in the expression of genes encoding kinases of the PI3K/Akt/mTOR signaling pathway. The obtained results confirm the role of redox-dependent regulation in the "reversal" of cancer cells resistance to cisplatin.
Subject(s)
Curcumin , Ovarian Neoplasms , Antioxidants/pharmacology , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Curcumin/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Humans , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
Expression of genes that plays a significant role in the control of cellular redox homeostasis was studied during the development of drug resistance of human ovarian adenocarcinoma SKOV-3 cells to cisplatin. It was found that the development of drug resistance was accompanied by enhanced expression of the genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1) and transcription factor Nrf2, as well as reduced expression of the gene encoding NOX5 isoform of NADPH oxidase. The results testify to redox-dependent development of the adaptive antioxidant response as an important process in the mechanism of formation of resistance to cisplatin.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , NADPH Oxidase 5/genetics , NF-E2-Related Factor 2/genetics , Catalase/genetics , Catalase/metabolism , Cell Line, Tumor , Female , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Homeostasis , Humans , NADPH Oxidase 5/antagonists & inhibitors , NADPH Oxidase 5/metabolism , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/metabolism , Ovary , Oxidation-Reduction , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Glutathione Peroxidase GPX1ABSTRACT
We studied the expression of peroxiredoxin genes (PRDX1, PRDX2, PRDX3, and PRDX6) in human erythroleukemia K652, human breast carcinoma MCF-7, and human ovarian carcinoma SKOV-3 cells during cisplatin resistance development. It was found that drug resistance formation was accompanied by a significant increase in the expression of PRDX1, PRDX2, PRDX3, PRDX6 genes in all cancer cell strains, which confirms the important contribution of redox-dependent mechanisms into the development of cisplatin resistance of cancer cells.
Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Leukemia, Erythroblastic, Acute/genetics , Ovarian Neoplasms/genetics , Peroxiredoxin III/genetics , Peroxiredoxin VI/genetics , Peroxiredoxins/genetics , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Carcinoma/drug therapy , Carcinoma/enzymology , Cell Line, Tumor , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Female , Gene Expression/drug effects , Humans , Leukemia, Erythroblastic, Acute/drug therapy , Leukemia, Erythroblastic, Acute/enzymology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/enzymology , Oxidative Stress , Peroxiredoxin III/metabolism , Peroxiredoxin VI/metabolism , Peroxiredoxins/metabolismABSTRACT
We studied the expression of genes encoding glutathione-S-transferase isoforms GSTP1-1, GSTA4-4, and GSTK1-1 during the development of the resistance of human erythroleukemia (K562), mammary adenocarcinoma (MCF-7) and ovary adenocarcinoma (SKOV-3) cells to cisplatin (CDDP). It was found that drug resistance development in all three strains of tumor cells is associated with significant increase in hGSTP1 and hGSTA4 gene expression, whereas increased hGSTK1 gene expression was detected only in resistant K562/CDDP and MCF-7/CDDP cells.
