title: Asterosaponin 1 induces endoplasmic reticulum stress-associated apoptosis in A549 human lung cancer cells.
abstract: Asterosaponin 1, a new cytostatic agent from starfish, possesses several bioactivities including an antitumor effect. The aim of this study was to investigate the potential anti-proliferative and pro-apoptotic activity of asterosaponin 1 in A549 human lung cancer cells, as well as the potential mechanisms. The results showed that asterosaponin 1 inhibited the proliferation of A549 cells in a dose-dependent manner, and the cytostatic activity resulted from the induction of apoptotic cell death. Asterosaponin 1 increased ER dilation and cytosolic Ca2+ concentration, and enhanced the expression of the ER molecular chaperones GRP78 and GRP94 in a dose- and time-dependent manner. In addition, asterosaponin 1 treated A549 cells exerted increased expression and activity of CHOP, caspase-4 and JNK, three essential ER-associated apoptotic molecules. In summary, these results demonstrated that asterosaponin 1 inhibits the proliferation of A549 cells through induction of ER stress-associated apoptosis, making asterosaponin 1 a candidate new anticancer drug for lung cancer therapy.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Zhao
authors.forename: Changliang
authors.initials: C
authors.lastname: Zhu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Ni
authors.forename: Tonggang
authors.initials: T
authors.lastname: Liu
authors.forename: Sanming
authors.initials: S
authors.lastname: Deng
authors.forename: Jinbo
authors.initials: J
authors.lastname: Zhao
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D011083:Polycyclic Compounds; D012503:Saponins; C515773:asterosaponin 1