title: Anti-Proliferative Effects of Evodiamine on Human Breast Cancer Cells.
abstract: Endocrine sensitivity, assessed by the expression of estrogen receptor (ER), has long been the predict factor to guide therapeutic decisions. Tamoxifen has been the most successful hormonal treatment in endocrine-sensitive breast cancer. However, in estrogen-insensitive cancer tamoxifen showed less effectiveness than in estrogen-sensitive cancer. It is interesting to develop new drugs against both hormone-sensitive and insensitive tumor. In this present study we examined anticancer effects of evodiamine extracted from the Chinese herb, Evodiae fructus, in estrogen-dependent and -independent human breast cancer cells, MCF-7 and MDA-MB-231 cells, respectively. Evodiamine inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with concentration of 1×10(-6) and 1×10(-5) M. Evodiamine also induced apoptosis via up-regulation of caspase 7 activation, PARP cleavage (Bik and Bax expression). The expression of ER α and β in protein and mRNA levels was down-regulated by evodiamine according to data from immunoblotting and RT-PCR analysis. Overall, our results indicate that evodiamine mediates degradation of ER and induces caspase-dependent pathway leading to inhibit proliferation of breast cancer cell lines. It suggests that evodiamine may in part mediate through ER-inhibitory pathway to inhibit breast cancer cell proliferation.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China ; The Center of General Education, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, Republic of China.
authors.forename: Kai-Lee
authors.initials: KL
authors.lastname: Wang
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Hsia
authors.forename: Jiun-Yih
authors.initials: JY
authors.lastname: Yeh
authors.forename: Shao-Chi
authors.initials: SC
authors.lastname: Cheng
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D053179:Caspase 7 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D011799:Quinazolines / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; D000077267:Fulvestrant; D004958:Estradiol; C049639:evodiamine; D053179:Caspase 7