Capsaicin induces apoptosis through ubiquitin-proteasome system dysfunction.
Capsaicin is an active component of red pepper having an antiproliferative effect in a variety of cancer cells, which recent evidence suggests due to its ability to induce apoptosis. However, the molecular mechanisms through which capsaicin induces apoptosis are not well understood. Here we demonstrate that capsaicin-induced apoptosis is mediated via the inhibition cellular proteasome function. Treatment of capsaicin to mouse neuro 2a cells results in the inhibition of proteasome activity in a dose- and time-dependent manner that seems to correlate with its effect on cell death. The effect of capsaicin on cellular proteasome function is indirect and probably mediated via the generation of oxidative stress. Exposure of capsaicin also causes increased accumulation of ubiquitinated proteins as wells as various target substrates of proteasome like p53 and Bax and p27. Like many other classical proteasome inhibitors, capsaicin also triggers the intrinsic pathway of apoptosis involving mitochondria and induces neurite outgrowth. Our results strongly support for the use of capsaicin as an anticancer drug.
Maity
Ranjan
R
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122 050, Haryana, India.
Sharma
Jaiprakash
J
Jana
Nihar Ranjan
NR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D045304:Cytochromes c; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; D002211:Capsaicin