title: The endogenous oxindole isatin induces apoptosis of MCF‑7 breast cancer cells through a mitochondrial pathway.
abstract: Isatin is an endogenous indole in mammalian tissues and fluids that is expected to have antitumor effects in human breast cancer cells. Human breast cancer cells (MCF-7) were exposed to isatin at various concentrations (0, 50, 100, 200 µmol/l) for 48 h. Apoptotic features were demonstrated by nuclei staining with Hoechst 33258 and flow cytometry. Bcl-2 and Bax mRNA were analyzed via reverse transcription-polymerase chain reaction. Bcl-2, Bax, the inhibitor of caspase-activated DNase (ICAD), and cytochrome c protein were analyzed by western blot analysis. Apoptosis, caspase-9 and -3 activation and mitochondrial depolarization were assayed by flow cytometry. The results showed that isatin induced apoptosis of MCF-7 cells. Furthermore, Bcl-2 expression was decreased and the ratio of Bcl-2 to Bax was significantly decreased by isatin. The mitochondrial transmembrane potential was markedly decreased and the release of cytochrome c into the cytosol was elevated following treatment with isatin. At the same time, caspase-9 and -3 were stimulated, followed by the degradation of ICAD, a caspase-3 substrate.
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao, Qingdao, Shandong 266011, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao, Qingdao, Shandong 266011, P.R. China.
authors.forename: Yanpin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao, Qingdao, Shandong 266011, P.R. China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007510:Isatin / Q000494:pharmacology*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007510:Isatin