title: The anti-tumor activity and mechanism of alkaloids from Aconitum szechenyianum Gay.
abstract: In the current study, the anti-tumor activity of Aconitum szechenyianum Gay alkaloids (ASA) and its mechanism of action were investigated. The result showed that ASA could induce apoptosis in HepG-2, Hela and A549 cells but not in normal human embryonic kidney 293A cells, and its apoptotic effect on A549 cells was stronger than those of HepG-2 and Hela cells. Moreover, the following study showed that ASA could up-regulate the expression levels of p38 and phosphorylated p38 MAPK, suggesting ASA-induced apoptosis was associated with the p38 MAPK mediated pathway. Furthermore, ASA could up-regulate TNF-R1 and DR5 via activation of p38 MAPK, thereby activating caspase 8, revealing the death receptor pathway was also involved in this process. In addition, ASA could led to a loss in the mitochondrial out membrane potential, up-regulate p53, phosphorylated p53 and Bax, down-regulate Bcl-2, release cytochrome c from the mitochondria to the cytoplasm, and activate caspase-9 and caspase-3 in A549 cells, which revealed that ASA could also induce apoptosis through the mitochondria mediated pathway. These results suggested that ASA played the anti-tumor role through the activation of p38 MAPK-, death receptor-, mitochondria- and caspase-dependent apoptotic pathways.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Yuede
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Landscape Architecture and Arts, Northwest A&F University, Yangling, Shaanxi, PR China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Forestry, Northwest A&F University, Yangling, Shaanxi, PR China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Ruiqiao
authors.initials: R
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address: wjingyu2004@126.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
mesh_terms: D031841:Aconitum / Q000737:chemistry*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Aconitum szechenyianum Gay alkaloids; Lung adenocarcinoma A549 cell; Signaling pathway