title: Evodiamine induces apoptosis and inhibits metastasis in MDA‑MB-231 human breast cancer cells in vitro and in vivo.
abstract: Breast cancer remains the leading cause of cancer-related deaths among women. Owing to high efficiency and low toxic effects, further exploration of natural compounds from Chinese herbal medicine may be an efficient approach for breast cancer drug discovery. In this study, we investigated the effects of evodiamine on the growth and metastasis of MDA-MB-231 human breast cancer cells in vitro and in vivo. In vitro, evodiamine inhibited cell migration and invasion abilities through downregulation of MMP-9, urokinase-type plasminogen activator (uPA) and uPAR expression. Evodiamine-induced G0/G1 arrest and apoptosis were associated with a decrease in Bcl-2, cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression and an increase in Bax and p27Kip1 expression. Moreover, evodiamine regulated p-ERK and p-p38 MAPK expression. Evodiamine-induced apoptosis was enhanced by its combination with the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. Evodiamine-inhibited metastasis was partly blocked by combination with PD98059 or SB203580. In vivo, the administration of evodiamine (10 mg/kg) significantly reduced tumor growth and pulmonary metastasis. These results demonstrate that evodiamine possesses antitumor activities via inhibition of cell migration and invasion, arrest of the cell cycle and induction of cell apoptosis in MDA-MB-231 cells.
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai 201203, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Du
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Qian-Mei
authors.initials: QM
authors.lastname: Zhou
authors.forename: Tian-Ling
authors.initials: TL
authors.lastname: Zhang
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C436291:CDKN1B protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D055293:Receptors, Urokinase Plasminogen Activator; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C049639:evodiamine; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9