Inhibitory activities of MG-132 towards proteasome complex 9

MG-132 acts as a peptide aldehyde effectively blocks the proteolytic activity of proteasome complex 9. Proteasome inhibitors including MG-132 have been shown to induce apoptotic cell death through formation of ROS. ROS formation and GSH depletion due to proteasome inhibitors may cause mitochondrial dysfunction and subsequent cytochrome C release, which leads to cell viability loss [ 1, 2].

Cell lines

A549 cells, human cervical HeLa cancer cells, HT-29 colon cancer cells, MG-63 osteosarcoma cell?etc.

Preparation method

The solubility of this compound in DMSO is >23.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

24-48 h

Applications

MG-132 is a membrane-permeable proteasome inhibitor. It is used to Induce neurite outgrowth in PC12 cells at 10 μM. MG132 dose dependently inhibited the growth of A549 cells with an IC50 of approximately 20 μM. MG-132 also reduced the growth of human cervical HeLa cancer cells with an IC50 of approximately 5 μM. Treatment with 0.5 μM MG-132 significantly decreased the growth of HeLa cells and induced cell death as well [3]. MG-132 inhibits the growth of HT-29 colon cancer cells via inducing G2/M cell cycle arrest [4], causes MG-63 osteosarcoma cell arrest at G2/M phase [5], prolongs the duration of G0/G1 arrest in MnCl2-treated A549 cells and induces a G1 arrest in gastric carcinoma cells [6].?

Animal models

C57BL mice

Dosage form

~10 ug/kg/day, injection from tail vein or belly

Preparation method

Powder dissolved in DMSO to prepare stock solution with 10 mg/ml, and working solution is diluted by PBS or Saline. pH equals to 7.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1.?Ling YH, Liebes L, Zou Y and Perez-Soler R. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells, 2003; 278: 33714–33723.

2.?Qiu JH, Asai A, Chi S, et al. Proteasome inhibitors induce cytochrome c-caspase-3-like protease-mediated apoptosis in cultured cortical neurons. J Neurosci 2000; 20: 259–265.

3.?YH. Han, WH. Park, MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level, Human and Experimental Toxicology, 29(7) 607–614.

4.?Wu WK, Wu YC, Yu L, et al. Induction of autophagy by proteasome inhibitor is associated with proliferative arrest in colon cancer cells. Biochem Biophys Res Commun 2008; 374: 258–263.

5.?Yan XB, Yang DS, Gao X, et al. Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132. Cell Biol Int 2007; 31: 1136–1143.

6.?ZhangW, Tong Q, Li S, Wang X andWang Q.MG-132 inhibits telomerase activity, induces apoptosis and G(1) arrest associated with upregulated p27kip1 expression and downregulated survivin expression in gastric carcinoma cells. Cancer Invest 2008; 26:1032–1036.