title: The tetraindole SK228 reverses the epithelial-to-mesenchymal transition of breast cancer cells by up-regulating members of the miR-200 family.
abstract: The results of recent studies have shown that metastasis, the most common malignancy and primary cause of mortality promoted by breast cancer in women, is associated with the epithelial-to-mesenchymal transition (EMT). The results of the current study show that SK228, a novel indole containing substance, exhibits anti-cancer activity. In addition, the effects of SK228 on the regulation of EMT in breast cancer cells as well as the underlying mechanism have been explored. SK228 was observed to induce a fibroblastoid to epithelial-like change in the appearance of various breast cancer cell lines and to suppress the migration and invasion of these cancer cells in vitro. Moreover, expression of E-cadherin was found to increase following SK228 treatment whereas ZEB1 expression was repressed. Expression of other major EMT inducers, including ZEB2, Slug and Twist1, is also repressed by SK228 as a consequence of up-regulation of members of the miR-200 family, especially miR-200c. The results of animal studies demonstrate that SK228 treatment leads to effective suppression of breast cancer growth and metastasis in vivo. The observations made in this investigation show that SK228 reverses the EMT process in breast cancer cells via an effect on the miR-200c/ZEB1/E-cadherin signalling pathway. In addition, the results of a detailed analysis of the in vivo anti-cancer activities of SK228, carried out using a breast cancer xenograft animal model, show that this substance is a potential chemotherapeutic agent for the treatment of breast cancer.
authors: Institute of Chemistry, Academia Sinica, Taipei, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Chie-Hong
authors: CH
authors: Wang
authors: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
authors: Chia-Ling
authors: CL
authors: Chen
authors: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
authors: Shivaji V
authors: SV
authors: More
authors: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors: Pei-Wen
authors: PW
authors: Hsiao
authors: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
authors: Wen-Chun
authors: WC
authors: Hung
authors: Institute of Chemistry, Academia Sinica, Taipei, Taiwan; Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors: Wen-Shan
authors: WS
authors: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D021381:Protein Transport; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D014992:Xylenes / Q000494:pharmacology*
chemical_list: C572350:1,4-bis(di(5-hydroxy-1H-indol-3-yl)methyl)benzene; D015820:Cadherins; D007211:Indoles; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014992:Xylenes