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Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells.
Free Radic Res. 2011 Apr; 45(4):431-8.FR

Abstract

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.

Authors+Show Affiliations

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21110780

Citation

Jung, Kyu Ho, and Jeen-Woo Park. "Suppression of Mitochondrial NADP(+)-dependent Isocitrate Dehydrogenase Activity Enhances Curcumin-induced Apoptosis in HCT116 Cells." Free Radical Research, vol. 45, no. 4, 2011, pp. 431-8.
Jung KH, Park JW. Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells. Free Radic Res. 2011;45(4):431-8.
Jung, K. H., & Park, J. W. (2011). Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells. Free Radical Research, 45(4), 431-8. https://doi.org/10.3109/10715762.2010.540574
Jung KH, Park JW. Suppression of Mitochondrial NADP(+)-dependent Isocitrate Dehydrogenase Activity Enhances Curcumin-induced Apoptosis in HCT116 Cells. Free Radic Res. 2011;45(4):431-8. PubMed PMID: 21110780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells. AU - Jung,Kyu Ho, AU - Park,Jeen-Woo, Y1 - 2010/11/29/ PY - 2010/11/30/entrez PY - 2010/11/30/pubmed PY - 2011/7/1/medline SP - 431 EP - 8 JF - Free radical research JO - Free Radic Res VL - 45 IS - 4 N2 - 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. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/21110780/Suppression_of_mitochondrial_NADP_+__dependent_isocitrate_dehydrogenase_activity_enhances_curcumin_induced_apoptosis_in_HCT116_cells_ L2 - https://www.tandfonline.com/doi/full/10.3109/10715762.2010.540574 DB - PRIME DP - Unbound Medicine ER -