Chao JI, Liu HF.
The blockage of surviving and securing expression increases
the cytochalasin B induced cell death and growth inhibition in
human cancer cells.
Mol Pharmacol. 2006 Jan;69(1):154-64
Molecular Anticancer Laboratory,
Institute of Pharmacology and Toxicology, College of Life
Sciences, Tzu Chi University, 701, Section 3, Chung-Yang Road,
Hualien 970, Taiwan. chaoji@mail.tcu.edu.tw
Survivin and securin proteins are
overexpressed in most cancer cells that have been shown to
regulate mitotic progression. In this study, we investigated the
roles of survivin and securin on cytochalasin B, a cytokinesis
blocker mediating the cytotoxicity and cell growth inhibition in
human cancer cells. The human lung carcinoma cell lines A549 and
H1299 highly expressed survivin proteins in mitosis and
concentrated on the midbodies during cytokinesis. Cytochalasin B
significantly decreased cell survival, inhibited cell growth,
increased the levels of G(2)/M fractions, and induced binuclei
formation in lung carcinoma cells; however, the survivin
proteins were concentration-dependently increased by 1 to 5
mug/ml cytochalasin B for 24 h. It is noteworthy that the
expression of securin proteins was decreased in cytochalasin
B-treated lung carcinoma cells. Transfection of 20 to 40 nM
survivin siRNA for 48 h significantly induced the formation of
multiple nuclei and apoptosis but decreased the levels of
survivin and securin proteins in A549 cells. Cotreatment with
survivin small interfering RNA (siRNA) and cytochalasin B
increased the cytotoxicity and cell growth inhibition. In
addition, the securin-null colorectal carcinoma cells were more
susceptible to the cytotoxicity after cytochalasin B and
survivin siRNA treatments than the securin-wild-type cells. As a
whole, our results indicate that the inhibition of survivin and
securin protein expression may increase the cell death and
growth inhibition after cytochalasin B treatment in human cancer
cells.
PMID: 16219911 |
