The blockage of survivin and securin expression increases the cytochalasin B-induced cell death and growth inhibition in human cancer cells.
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.
Chao
Jui-I
JI
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
Liu
Huei-Fang
HF
D002453:Cell Cycle; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D003571:Cytochalasin B / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000473:pathology; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering; D064249:Securin; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; D000077022:Survivin; C578002:pituitary tumor-transforming protein 1, human; D003571:Cytochalasin B