title: Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.
abstract: Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: S-W
authors.initials: SW
authors.lastname: Ip
authors.forename: S-H
authors.initials: SH
authors.lastname: Lan
authors.forename: H-F
authors.initials: HF
authors.lastname: Lu
authors.forename: A-C
authors.initials: AC
authors.lastname: Huang
authors.forename: J-S
authors.initials: JS
authors.lastname: Yang
authors.forename: J-P
authors.initials: JP
authors.lastname: Lin
authors.forename: H-Y
authors.initials: HY
authors.lastname: Huang
authors.forename: J-C
authors.initials: JC
authors.lastname: Lien
authors.forename: C-C
authors.initials: CC
authors.lastname: Ho
authors.forename: C-F
authors.initials: CF
authors.lastname: Chiu
authors.forename: Wg
authors.initials: W
authors.lastname: Wood
authors.forename: J-G
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002277:Carcinoma; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D020169:Caspases; D002211:Capsaicin; D002118:Calcium