title: Fangchinoline inhibits cell proliferation via Akt/GSK-3beta/ cyclin D1 signaling and induces apoptosis in MDA-MB-231 breast cancer cells.
abstract: Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Functional Genomics Lab, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China E-mail : cdwhust@163.com, fzsongcq@163.com.
authors.forename: Chang-Dong
authors.initials: CD
authors.lastname: Wang
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Yuan
authors.forename: You-Quan
authors.initials: YQ
authors.lastname: Bu
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Wu
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Wan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zu
authors.forename: Ge-Li
authors.initials: GL
authors.lastname: Liu
authors.forename: Fang-Zhou
authors.initials: FZ
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D044182:Benzylisoquinolines; C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; C060802:fangchinoline; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3