Bone morphogenetic protein signalling is required for the anti-mitogenic effect of the proteasome inhibitor MG-132 on colon cancer cells.

British Journal of Pharmacology
W K K WuC H Cho

Abstract

Inhibition of proteasome has been emerging as a promising approach in pathway-directed cancer therapy. Bone morphogenetic protein (BMP) signalling, which is known to be regulated by the ubiquitin-proteasome pathway in osteoblasts, plays a crucial role in the suppression of gastrointestinal carcinogenesis. Here we sought to elucidate the anti-mitogenic effect of a proteasome inhibitor in relation to BMP signalling in colon cancer. The effects of the proteasome inhibitor MG-132 on proliferation of SW1116 and HT-29 colon cancer cells were determined by [(3)H]-thymidine incorporation and colony-formation assay. The involvement of BMP signalling in the action of MG-132 was elucidated by western blot, real-time PCR, immunofluorescence and RNA interference. MG-132 significantly suppressed the proliferation of colon cancer SW1116 and HT-29 cells. In this regard, MG-132 activated BMP signalling and this was manifested as an increase in Smad1/5/8 phosphorylation and upregulation of p21(Waf1/Cip1) and p27(Kip1) expression. Knockdown of BMP receptor II abolished Smad1/5/8 phosphorylation, the induction of p21(Waf1/Cip1) and p27(Kip1) and inhibition of cell proliferation induced by MG-132. Further analysis revealed that MG-132 upregulated t...Continue Reading

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Citations

Jan 12, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Liang WangYan Zhang
Jan 16, 2013·The International Journal of Developmental Biology·Consuelo PastenJosé E García-Arrarás
Jan 5, 2013·Critical Reviews in Oncology/hematology·William K K WuJun Yu
Feb 6, 2010·Cancer Letters·William Ka Kei WuJoseph Jao Yiu Sung
Sep 22, 2009·The Journal of Surgical Research·Jui-yu ChenHerbert Chen
Jun 4, 2010·International Journal of Cancer. Journal International Du Cancer·William K K WuChi H Cho
Jul 22, 2008·Biochemical and Biophysical Research Communications·William Ka Kei WuChi Hin Cho
Jun 23, 2009·Biochemical and Biophysical Research Communications·William Ka Kei WuJoseph Jao Yiu Sung
Mar 18, 2009·Biochemical and Biophysical Research Communications·Ya Chun WuChi Hin Cho
Jul 10, 2009·Clinical Orthopaedics and Related Research·Bruno DohinReggie Hamdy
Aug 26, 2014·Biological Chemistry·George S KaragiannisEleftherios P Diamandis
Nov 29, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S Kamali ZonouziN Rezaei

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