title: Synthesis and evaluation of the cytotoxicities of tetraindoles: observation that the 5-hydroxy tetraindole (SK228) induces G₂ arrest and apoptosis in human breast cancer cells.
abstract: Current chemical and biological interest in indole-3-carbinol (I3C) and its metabolites has resulted in the discovery of new biologically active indoles. As part of a program aimed at the development of indole analogues, tetraindoles 1-15 were prepared and their antiproliferative effects on human breast cancer cells were evaluated. The results show that the 5-hydroxy-tetraindole 8 (SK228) has optimum antiproliferative activity against breast adenocarcinoma (MCF 7 and MDA-MB-231) cells and that this activity involves G(2)-phase arrest of the cell cycle with a distinctive increase in the expression of cyclin B1 and phospho-cdc2. Further observations suggest that 5-hydroxy-tetraindole 8 induces apoptosis through externalization of membrane phosphatidylserine, DNA fragmentation, and activation of caspase-3. Given the fact that I3C and its metabolites have been shown to improve therapeutic efficacy and to have a broad range of antitumor activities in human cancer cells, the current findings have important pharmacological relevance as they open a promising route to the development of a potential chemotherapeutic application of tetraindoles as agents for the treatment of breast cancer.
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan. wenshan@chem.sinica.edu.tw
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Li
authors.forename: Chie-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Shengkai
authors.initials: S
authors.lastname: Ko
authors.forename: Tzu Ting
authors.initials: TT
authors.lastname: Chang
authors.forename: Ya Ching
authors.initials: YC
authors.lastname: Jen
authors.forename: Ching-Fa
authors.initials: CF
authors.lastname: Yao
authors.forename: Shivaji V
authors.initials: SV
authors.lastname: More
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Jao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C572350:1,4-bis(di(5-hydroxy-1H-indol-3-yl)methyl)benzene; D000970:Antineoplastic Agents; D007211:Indoles; D014992:Xylenes