title: Galangin potentiates human breast cancer to apoptosis induced by TRAIL through activating AMPK.
abstract: Breast cancer is reported as the most frequent tumor with limited treatments among the female worldwide. Galangin, a natural active compound 3, 5, 7-trihydroxyflavone, is a type of bioflavonoid isolated from the Alpinia galangal root and suggested to induce apoptosis in various cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective anti-tumor agent for human breast cancer. Promoted expression of CHOP, a down-streaming transcription factor for endoplasmic reticulum stress (ER stress), enhanced death factor 4 (DR4) activity and accelerated reactive oxygen species (ROS) as well as cell death. Adenosine monophosphate-activated protein kinase (AMPK) is crucial for various cancers mortality. In the present study, galangin regulated ER stress to augment CHOP and DR4 expression levels, sensitizing TRAIL activity, leading to human breast cancer cell apoptosis through Caspase-3 activation, which was associated with AMPK phosphorylation. In addition, AMPK inhibition and silence reduced anti-cancer activity of galangin and TRAIL in combinational treatment. Hence, our study indicated that galangin could effectively stimulate human breast cancer cells to TRAIL-induced apoptosis through TRAIL/Caspase-3/AMPK signaling pathway. AMPK signaling pathway activation by galangin might be of benefit for promoting the effects of TRAIL-regulated anti-tumor therapeutic strategy.
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University,No.6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu, 223001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Lianshui County People's Hospital, No.6 Hongridadao, Huai'an, Jiangsu, 223001, China.
authors.forename: Chong-Yang
authors.initials: CY
authors.lastname: Yan
authors.affiliation: Huai'an Industrial Park People's Hospital, Panyuan Road, Qingpu District, Huai'an, Jiangsu, 223001, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhou
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University,No.6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu, 223001, China. Electronic address: zhenlinlindoc@foxmail.com.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Zhen
mesh_terms: D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C037032:galangin; D000263:Adenylate Kinase
keywords: AMPK; Apoptosis; Breast cancer; Galangin; TRAIL