Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells.

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.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Jung KH,Park JW

doi

10.3109/10715762.2010.540574

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

431-8

issue

4

eissn

1071-5762

issn

1029-2470

journal_volume

45

pub_type

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