Identification of a novel blocker of IkappaBalpha kinase activation that enhances apoptosis and inhibits proliferation and invasion by suppressing nuclear factor-kappaB

Molecular Cancer Therapeutics
Bokyung SungBharat B Aggarwal

Abstract

3,4-dihydroxybenzalacetone (DBL) is a polyphenol derived from the medicinal plant Chaga [Inonotus obliquus (persoon) Pilat]. Although Chaga is used in Russia folk medicine to treat tumors, very little is known about its mechanism of action. Because most genes involved in inflammation, antiapoptosis, and cell proliferation are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we postulated that DBL activity is mediated via modulation of the NF-kappaB activation pathway. We investigated the effects of DBL on NF-kappaB activation by electrophoretic mobility shift assay and on NF-kappaB-regulated gene expression by Western blot analysis. We found that DBL suppressed NF-kappaB activation by a wide variety of inflammatory agents, including tumor necrosis factor (TNF), interleukin-1beta, epidermal growth factor, okadaic acid, phorbol 12-myristate 13-acetate, and lipopolysaccharide. The suppression was not cell type specific and inhibited both inducible and constitutive NF-kappaB activation. DBL did not interfere with the binding of NF-kappaB to DNA but rather inhibited IkappaBalpha kinase activity, IkappaBalpha phosphorylation and degradation, p65 phosphorylation, and translocation. DBL also suppressed the expre...Continue Reading

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Citations

Dec 31, 2010·Pharmaceutical Research·Rubi MahatoKun Cheng
Oct 12, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lou ZhongQingsheng You
Sep 25, 2010·Breast Cancer Research : BCR·Bin Qin, Kun Cheng
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Jun 15, 2010·Viruses·Han Hsi WongYaohe Wang
Jan 30, 2013·Molecular and Cellular Biochemistry·Zhang PengLiu Ying
Jun 11, 2017·Scientific Reports·Pengfei JinWeiguo Miao
Jun 10, 2011·Free Radical Research·Bokyung SungBharat B Aggarwal
Jan 17, 2016·Clinical and Experimental Pharmacology & Physiology·Qingyu ZhouShufeng Zhou

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