title: Glaucocalyxin A activates FasL and induces apoptosis through activation of the JNK pathway in human breast cancer cells.
abstract: THis study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as 1 μM in MCF-7 and 4 μM in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu, China E-mail : zhenlungu.2003@163.com, zubinzhang.2008@163.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Jiang
authors.forename: Zhen-Lun
authors.initials: ZL
authors.lastname: Gu
authors.forename: Zu-Bin
authors.initials: ZB
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D061986:MCF-7 Cells; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D045786:Diterpenes, Kaurane; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C055124:glaucocalyxin A; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases