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

作者：Chiang Nai Jung; Lin Ching I; Liou Jing Ping; Kuo Ching Chuan; Chang Chi Yen; Chen Li Tzong; Chang Jang Yang^*

来源：PLos One, 2013, 8(3): e58953.

DOI：10.1371/journal.pone.0058953

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%26apos;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 G(2)-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.

• 出版日期2013-3-12