Inhibition of Proteasomal Function by Curcumin Induces Apoptosis through Mitochondrial Pathway

Nihar Ranjan Jana,Priyanka Dikshit,Anand Goswami,Nobuyuki Nukina

doi:10.1074/jbc.m310369200

Abstract

Curcumin is a natural polyphenolic compound having an antiproliferative property, which recent evidence suggests is due to its ability to induce apoptosis. However, the molecular mechanisms through which curcumin induces apoptosis are not fully understood. Here, we report that the curcumin-induced apoptosis is mediated through the impairment of the ubiquitin-proteasome system. Exposure of curcumin to the mouse neuro 2a cells causes a dose-dependent decrease in proteasome activity and an increase in ubiquitinated proteins. Curcumin exposure also decreases the turnover of the destabilized enhanced green fluorescence protein, a model substrate for proteasome and cellular p53 protein. Like other proteasome inhibitors, curcumin targets proliferative cells more efficiently than differentiated cells and induces apoptosis via mitochondrial pathways. Addition of curcumin to neuro 2a cells induces a rapid decrease in mitochondrial membrane potential and the release of cytochrome c into cytosol, followed by activation of caspase-9 and caspase-3.

Highlights

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene3,5-dione) is the major yellow pigment extracted from turmeric, a commonly used spice, derived from the rhizome of the plant Curcuma longa
Curcumin Kills Growing Neuro 2a Cells More Rapidly than Differentiated Neuro 2a Cells—Curcumin has been reported to inhibit the proliferation of various tumor cells, but it was not known whether the sensitivity of curcumin differs between dividing and differentiated cell
Recent evidence suggests that the curcumin has chemopreventive and anti-tumor activities because of its ability to induce apoptosis

Summary

Introduction

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene3,5-dione) is the major yellow pigment extracted from turmeric, a commonly used spice, derived from the rhizome of the plant Curcuma longa. Exposure of curcumin to the mouse neuro 2a cells causes a dose-dependent decrease in proteasome activity and an increase in ubiquitinated proteins. Addition of curcumin to neuro 2a cells induces a rapid decrease in mitochondrial membrane potential and the release of cytochrome c into cytosol, followed by activation of caspase-9 and caspase-3.

Results

Conclusion