Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways |
| |
Authors: | Mi-Ja Lee Keun-Hong Kee Chae-Hong Suh Sung-Chul Lim Seon-Hee Oh |
| |
Institution: | 1. Department of Pathology, College of Medicine, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea;2. Research Center for Resistant Cells, College of Medicine, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea |
| |
Abstract: | Capsaicin, a pungent compound found in hot chili peppers, induces apoptotic cell death in various cell lines, however, the precise apoptosis signaling pathway is unknown. Here, we investigated capsaicin-induced apoptotic signaling in the human breast cell line MCF10A and found that it involves both endoplasmic reticulum (ER) stress and calpain activation. Capsaicin inhibited growth in a dose-dependent manner and induced apoptotic nuclear changes in MCF10A cells. Capsaicin also induced degradation of tumor suppressor p53; this effect was enhanced by the ER stressor tunicamycin. The proteasome inhibitor MG132 completely blocked capsaicin-induced p53 degradation and enhanced apoptotic cell death. Capsaicin treatment triggered ER stress by increasing levels of IRE1, GADD153/Chop, GRP78/Bip, and activated caspase-4. It led to an increase in cytosolic Ca2+, calpain activation, loss of the mitochondrial transmembrane potential, release of mitochondrial cytochrome c, and caspase-9 and -7 activation. Furthermore, capsaicin-induced the mitochondrial apoptotic pathway through calpain-mediated Bid translocation to the mitochondria and nuclear translocation of apoptosis-inducing factor (AIF). Capsaicin-induced caspase-9, Bid cleavage, and AIF translocation were blocked by calpeptin, and BAPTA and calpeptin attenuated calpain activation and Bid cleavage. Thus, both ER stress- and mitochondria-mediated death pathways are involved in capsaicin-induced apoptosis. |
| |
Keywords: | ER endoplasmic reticulum IRE1 inositol-requiring 1 enzyme AIF apoptosis-inducing factor BAPTA 2-bis(o-aminophenoxy) ethane-N N N&prime N&prime -tetraacetic acid MMP mitochondrial transmembrane potential Cytc cytochrome c PARP poly(ADP-ribose) polymerase MTT 3-(4 5-dimetylthiazole-2-yl)-2 5-diphenyltetrazolium bromide |
本文献已被 ScienceDirect 等数据库收录! |
|