title: A novel synthetic microtubule inhibitor, MPT0B214 exhibits antitumor activity in human tumor cells through mitochondria-dependent intrinsic pathway.
abstract: Agents that interfere with mitotic progression by disturbing microtubule dynamics are commonly used for cancer treatment. Previously, a series of aroylquinolone regioisomers as novel microtubule inhibitors were discovered. One of these new compounds, MPT0B214 inhibited tubulin polymerization through strongly binding to the tubulin's colchicine-binding site and had cytotoxic activity in a variety of human tumor cell lines. After treatment with MPT0B214, KB cells were arrested in the G2-M phase before cell death occurred, which were associated with upregulation of cyclin B1, dephosphorylation of Cdc2, phosphorylation of Cdc25C and elevated expression of the mitotic marker MPM-2. Furthermore, the compound induced apoptotic cell death through mitochondria/caspase 9-dependent pathway. Notably, several KB-derived multidrug-resistant cancer cell lines were also sensitive to MPT0B214 treatment. These findings showed that MPT0B214 is a potential compound in the treatment of various malignancies.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
authors.forename: Nai-Jung
authors.initials: NJ
authors.lastname: Chiang
authors.forename: Ching-I
authors.initials: CI
authors.lastname: Lin
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Chang
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001665:Binding Sites; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C583711:5-amino-6-methoxy-2-(3',4',5'-trimethoxybenzoyl)quinoline; D018435:ATP Binding Cassette Transporter, Subfamily B; D000634:Aminoquinolines; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D050257:Tubulin Modulators; D045304:Cytochromes c; D003078:Colchicine
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