Induction of autophagy by proteasome inhibitor is associated with proliferative arrest in colon cancer cells

Journal Article · Fri Sep 19 04:00:00 EDT 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.07.031· OSTI ID:21143869

Wu, William Ka Kei ^[1]; Yachun, Wu ^[1]; Le, Yu; Zhijie, Li ^[1]; Sung, Joseph Jao Yiu ^[2]; Cho, C H ^[1]

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1. Department of Pharmacology, Basic Medical Sciences Building, Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)
2. Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong (China)

The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Blockade of UPS by proteasome inhibitors has been shown to activate autophagy. Recent evidence also suggests that proteasome inhibitors may inhibit cancer growth. In this study, the effect of a proteasome inhibitor MG-132 on the proliferation and autophagy of cultured colon cancer cells (HT-29) was elucidated. Results showed that MG-132 inhibited HT-29 cell proliferation and induced G{sub 2}/M cell cycle arrest which was associated with the formation of LC3{sup +} autophagic vacuoles and the accumulation of acidic vesicular organelles. MG-132 also increased the protein expression of LC3-I and -II in a time-dependent manner. In this connection, 3-methyladenine, a Class III phosphoinositide 3-kinase inhibitor, significantly abolished the formation of LC3{sup +} autophagic vacuoles and the expression of LC3-II but not LC3-I induced by MG-132. Taken together, this study demonstrates that inhibition of proteasome in colon cancer cells lowers cell proliferation and activates autophagy. This discovery may shed a new light on the novel function of proteasome in the regulation of autophagy and proliferation in colon cancer cells.

• OSTI ID: 21143869
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 374; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CONSTITUENTS
CELL CYCLE
CELL PROLIFERATION
GENE REGULATION
LARGE INTESTINE
NEOPLASMS
PROTEINS
TIME DEPENDENCE