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Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Potentiates TRAIL-induced Apoptosis of Human Colorectal Carcinoma Cells Through Inhibition of NF-kappaB

Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Potentiates TRAIL-induced Apoptosis of Human Colorectal Carcinoma Cells Through Inhibition of NF-kappaB

A C Williams, H Smartt, A M H-Zadeh, M Macfarlane, C Paraskeva, T J Collard

Cell Death Differ. 2007 Jan;14(1):137-45.

PMID: 16645643

Abstract:

There is growing evidence that the insulin-like growth factor-binding protein 3 (IGFBP-3) can have IGF-independent effects on cell growth. However, despite the fact that IGFBP-3 has been reported to be both antiproliferative and proapoptotic, the molecular mechanisms underlying the action of IGFBP-3 have not been elucidated. We report that although addition of IGFBP-3 (either synthetic or secreted protein) had no effect on cell survival, IGFBP-3 (100 ng/ml) significantly enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cell death in colonic carcinoma-derived cell lines (20-30% depending on cell line), whereas it had no effect on the survival of the TRAIL-resistant adenoma-derived cells. Both addition of IGFBP-3 protein to cell cultures or enforced expression of IGFBP-3 in the HT29 carcinoma cell line inhibited nuclear factor kappa B (NF-kappaB) activation in response to the induction of apoptosis by TRAIL. We propose that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an adjuvant in the treatment of colon cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413300	Insulin-Like Growth Factor Binding Protein-3 human			Price

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