A Novel Synthetic Microtubule Inhibitor, MPT0B214 Exhibits Antitumor Activity in Human Tumor Cells through Mitochondria-Dependent Intrinsic Pathway

Nai Jung Chiang, Ching I. Lin, Jing Ping Liou, Ching Chuan Kuo, Chi Yen Chang, Li Tzong Chen, Jang Yang Chang

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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.

Original languageEnglish
Article numbere58953
JournalPloS one
Volume8
Issue number3
DOIs
Publication statusPublished - 2013 Mar 12

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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