title: Novel mechanism of harmaline on inducing G2/M cell cycle arrest and apoptosis by up-regulating Fas/FasL in SGC-7901 cells.
abstract: Harmaline (HAR), a natural occurrence β-carboline alkaloid, was isolated from the seeds of Peganum harmala and exhibited potent antitumor effect. In this study, the anti-gastric tumor effects of HAR were firstly investigated in vitro and in vivo. The results strongly showed that HAR could inhibit tumor cell proliferation and induce G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. HAR could up-regulate the expressions of cell cycle-related proteins of p-Cdc2, p21, p-p53, Cyclin B and down-regulate the expression of p-Cdc25C. In addition, HAR could up-regulate the expressions of Fas/FasL, activated Caspase-8 and Caspase-3. Moreover, blocking Fas/FasL signaling could markedly inhibit the apoptosis caused by HAR, suggesting that Fas/FasL mediated pathways were involved in HAR-induced apoptosis. Interestingly, HAR could also exert on antitumor activity with a dose of 15 mg/kg/day in vivo, which was also related with cell cycle arrest. These new findings provided a framework for further exploration of HAR which possess the potential antitumor activity by inducing cell cycle arrest and apoptosis.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Huangshan Jingzhi Pharmaceutical Company of Nanjing Tongrentang Group, Huangshan 245999, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Xinjiang Production &Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim 843300, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiangjiu
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006246:Harmaline / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D032443:Peganum / Q000737:chemistry / Q000378:metabolism; D012639:Seeds / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D006246:Harmaline