These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 6,7-Dimethoxy-3-(3-methoxyphenyl)isoquinolin-1-amine induces mitotic arrest and apoptotic cell death through the activation of spindle assembly checkpoint in human cervical cancer cells.
    Author: Chung KS, Choi HE, Shin JS, Cho YW, Choi JH, Cho WJ, Lee KT.
    Journal: Carcinogenesis; 2013 Aug; 34(8):1852-60. PubMed ID: 23615402.
    Abstract:
    Previously, we reported that 6,7-dimethoxy-3-(3-methoxyphenyl)isoquinolin-1-amine (CWJ-082) has potent cytotoxic effects on various cancer cells, but the underlying molecular mechanism responsible was not determined. In the present study, CWJ-082 caused cervical cancer cell cycle arrest at the G2/M phase and subsequent caspase-dependent apoptosis. The mitotic arrest caused by CWJ-082 found to be due to increases in the activation of cyclin-dependent kinase 1/cyclin B1 complex and the phosphorylation of histone H3. In addition, CWJ-082 induced the phosphorylation of BubR1 and the association between mitotic arrest deficient 2 (Mad2) and cell division cycle protein 20. These findings suggested that CWJ-082 activated the mitotic spindle checkpoint. Furthermore, knockdown of the spindle checkpoint proteins BubR1 or Mad2 using specific small interfering RNAs significantly reduced CWJ-082-induced mitotic cell accumulation and apoptosis. In addition, CWJ-082 induced the appearance of spindle abnormalities by inducing α-tubulin polymerization. In BALB/c(nu/nu) mice bearing a HeLa xenograft, CWJ-082 significantly inhibited tumor growth. Taken together, these results suggest that CWJ-082 inhibits cell growth via mitotic arrest by activating the mitotic spindle checkpoint and by inducing α-tubulin polymerization and that these events ultimately lead to the apoptosis of human cervical cancer cells and inhibit tumor growth in HeLa xenograft mice.
    [Abstract] [Full Text] [Related] [New Search]