Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus.
Capsaicin is widely used as a food additive and as an analgesic agent. Besides its well-known role in nociception, which is mediated by vanilloid receptor 1 specifically expressed in dorsal root ganglion neurons, capsaicin has also been considered as a potential anticancer agent, as it inhibits cell proliferation and induces apoptosis in various types of cancer cells. Here we identified a new molecular target of capsaicin from human myeloid leukemia cells. We show that capsaicin binds to prohibitin (PHB) 2, which is normally localized to the inner mitochondrial membrane, and induces its translocation to the nucleus. PHB2 is implicated in the maintenance of mitochondrial morphology and the control of apoptosis. We also provide evidence suggesting that capsaicin causes apoptosis directly through the mitochondria and that PHB2 contributes to capsaicin-induced apoptosis at multiple levels. This work will serve as an important foundation for further understanding of anticancer activity of capsaicin.
Kuramori
Chikanori
C
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Azuma
Motoki
M
Kume
Kanako
K
Kaneko
Yuki
Y
Inoue
Atsushi
A
Yamaguchi
Yuki
Y
Kabe
Yasuaki
Y
Hosoya
Takamitsu
T
Kizaki
Masahiro
M
Suematsu
Makoto
M
Handa
Hiroshi
H
D021581:Active Transport, Cell Nucleus; D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism; D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis; D002211:Capsaicin / Q000378:metabolism* / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism*
D033742:Adenine Nucleotide Translocator 2; D000700:Analgesics; C000717328:PHB protein, human; C000717331:PHB2 protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D045304:Cytochromes c; D002211:Capsaicin