title: Fangchinoline inhibits breast adenocarcinoma proliferation by inducing apoptosis.
abstract: Radix Stephaniae tetrandrae, which contains tetrandrine (Tet) and fangchinoline, is traditionally used as an analgesic, antirheumatic, and antihypertensive drug in China. In this study, we investigated its effect on breast cancer cell proliferation and its potential mechanism of action in vitro. Treatment of cells with fangchinoline significantly inhibited MDA-MB-231 cell proliferation in a concentration- and time-dependent manner. To define the mechanism underlying the antiproliferative effects of fangchinoline, we studied its effects on critical molecular events known to regulate the apoptotic machinery. Specifically, we addressed the potential of fangchinoline to induce apoptosis of breast cancer cells. Fangchinoline induced internucleosomal DNA fragmentation, chromatin condensation, activation of caspases-3, -8, and -9, and cleavage of poly(ADP ribose) polymerase, as well as enhanced mitochondrial cytochrome c release. Furthermore, fangchinoline increased the expression of the proapoptotic protein B cell lymphoma-2 associated X (Bax) and decreased the expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2). In addition, the proliferation-inhibitory effect of fangchinoline was associated with decreased levels of phosphorylated Akt. Our results indicate that fangchinoline can inhibit breast cancer cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway and decreasing phosphorylated Akt. Thus fangchinoline may be a novel agent that can potentially be developed clinically to target human malignancies.
authors: Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China.
authors: Zhi-Bo
authors: ZB
authors: Xing
authors: Lei
authors: L
authors: Yao
authors: Guo-Qiang
authors: GQ
authors: Zhang
authors: Xian-Yu
authors: XY
authors: Zhang
authors: You-Xue
authors: YX
authors: Zhang
authors: Da
authors: D
authors: Pang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D031609:Stephania tetrandra / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C060802:fangchinoline; D020169:Caspases