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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 - Mar 12 2013

Fingerprint

Mitochondria
tubulin
Human Activities
Microtubules
microtubules
cell death
Tumors
mitochondria
Cells
cell lines
caspase-9
dephosphorylation
colchicine
cyclins
Cell death
Tubulin
polymerization
mitosis
binding sites
Neoplasms

ASJC Scopus subject areas

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

Cite this

A Novel Synthetic Microtubule Inhibitor, MPT0B214 Exhibits Antitumor Activity in Human Tumor Cells through Mitochondria-Dependent Intrinsic Pathway. / Chiang, Nai Jung; Lin, Ching I.; Liou, Jing Ping; Kuo, Ching Chuan; Chang, Chi Yen; Chen, Li Tzong; Chang, Jang Yang.

In: PLoS One, Vol. 8, No. 3, e58953, 12.03.2013.

Research output: Contribution to journalArticle

Chiang, Nai Jung ; Lin, Ching I. ; Liou, Jing Ping ; Kuo, Ching Chuan ; Chang, Chi Yen ; Chen, Li Tzong ; Chang, Jang Yang. / A Novel Synthetic Microtubule Inhibitor, MPT0B214 Exhibits Antitumor Activity in Human Tumor Cells through Mitochondria-Dependent Intrinsic Pathway. In: PLoS One. 2013 ; Vol. 8, No. 3.
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