Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway.
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.
Jana
Nihar Ranjan
NR
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122050, India. nihar@nbrc.ac.in
Dikshit
Priyanka
P
Goswami
Anand
A
Nukina
Nobuyuki
N
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009097:Multienzyme Complexes / Q000187:drug effects*; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin