Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells.
Curcumin is a polyphenol derived from the plant Curcuma longa that induces apoptotic cell death in malignant cancer cell lines. It has been shown previously that mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) plays an essential role in defense against oxidative stress by supplying NADPH for antioxidant systems. This study demonstrates that curcumin decreased the activity of IDPm, both as a purified enzyme and in cultured cells. It also shows that curcumin-induced apoptosis in the colon cancer cell line HCT116 is significantly enhanced by suppression of IDPm activity. Transfection of HCT116 cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing cellular susceptibility to curcumin-induced apoptosis, as reflected by DNA fragmentation, cellular redox status, mitochondria dysfunction and modulation of apoptotic marker proteins. Together, these results suggest that application of curcumin together with IDPm siRNA may be an effective combination modality in the treatment of cancer.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.
Kyu Ho
KH
Jung
Jeen-Woo
JW
Park
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects; D004357:Drug Synergism; D004926:Escherichia coli; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009249:NADP / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D009249:NADP; D007521:Isocitrate Dehydrogenase; D003474:Curcumin