Journal Article

Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells

Gavin P. Collett and Frederick C. Campbell

in Carcinogenesis

Volume 27, issue 6, pages 1285-1291
Published in print June 2006 | ISSN: 0143-3334
Published online February 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi368
Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells

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Curcumin, the yellow pigment in the spice turmeric, has potent chemopreventive activities that involve diverse molecular pathways. It is widely believed that curcumin pro-apoptotic properties are mediated by downregulation of NF kappa B (NFκB). The p65/RelA subunit of NFκB may influence cell death, in part by activation of NFκB anti-apoptotic target genes including X-linked inhibitor of apoptosis (XIAP), A20, bcl-xL and inhibition of sustained activation of c-Jun N-terminal kinase (JNK). We have shown previously that curcumin inhibits NFκB, activates JNK and promotes apoptosis in HCT116 colorectal cancer cells. Here, we show that forced overexpression of p65 does not affect curcumin-induced JNK activation. Indeed, overexpression of p65 enhanced curcumin-mediated apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and poly(ADP-ribose) polymerase (PARP) cleavage. This potentiating effect of p65 upon curcumin-mediated apoptosis was reversed by transfection of cells with an IκB super-repressor (ΔNIκB). Curcumin treatment inhibited expression of NFκB anti-apoptotic target genes in mock-transfected and in p65-overexpressing HCT116 cells, although expression levels remained higher in the latter. Taken together, these results show that curcumin-mediated activation of JNK or induction of apoptosis does not require inhibition of p65. Furthermore, curcumin/p65 synergy in promotion of apoptosis cannot be attributed to active repression of NFκB anti-apoptotic genes.

Keywords: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; JNK, c-jun N-terminal kinase; MKK, mitogen-activated protein kinase kinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide; NFκB, nuclear factor kappa B; PARP, poly (ADP-ribose) polymerase; PKC, protein kinase C; XIAP, X-linked inhibitor of apoptosis

Journal Article.  4828 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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