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Exploring the Relationship between the Inhibition Selectivity and the Apoptosis of Roscovitine-Treated Cancer Cells

DOI: 10.1155/2013/389390

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Abstract:

The antitumor activity of roscovitine was tested in four cervical carcinoma cells: C33A, HCE-1, HeLa, and SiHa. The effects of roscovitine on ATP Lite assay, cell cycle, and apoptosis were assessed. The Sub-G1 DNA content occurred great increasing, and this indicates that apoptosis was induced quickly in HeLa cells, but slowly in the other cells. The morphological observation results showed that roscovitine induced apoptosis and cell death in the cervical carcinoma cells. Results revealed that roscovitine exhibited selective cytotoxicity towards 4 cervical carcinoma cells, and the cells showed different morphologic and apoptotic changes at the same concentration. It was estimated that cervical carcinoma cells responded differently to roscovitine because of differences in apoptotic and genetic background in different cervical carcinoma cells. This study suggested that roscovitine had the potential to be a chemotherapeutic agent against cervical carcinoma. 1. Introduction Cyclin-dependent kinase inhibitors have the potential to induce cell cycle arrest and apoptosis in cancer cells [1]. Roscovitine, a potent and selective inhibitor of Cdk2 and Cdc2, has demonstrated selective inhibition of Cdk enzymes over related kinases. It has been reported that roscovitine does cause not only cell cycle arrest, but also apoptosis in cancer cells [2, 3]. In in vitro study, it has been shown that roscovitine has cytotoxic activity against a lot of human tumor cells, as well as in tumor xenograft models [4, 5]. Roscovitine is currently undergoing phase II clinical trials as a treatment for nonsmall cell lung cancer and nasopharyngeal cancer [6, 7]. In this study, we investigated whether roscovitine could inhibit the tumor growth and exhibit cytotoxicity in cervical carcinoma cell lines: C33A, HCE-1, HeLa, and SiHa. In addition, we are interested in elucidating the biochemistry of apoptosis of roscovitine on these cell lines. Our data showed that roscovitine can inhibit tumor cell proliferation in dose- and time-dependent manner in cervical carcinoma cells. Roscovitine can induce cell cycle arrest and apoptosis in 4 cervical cells but showed selective sensitivity. We estimated that cervical carcinoma cells responded differently to roscovitine because of differences in apoptotic and genetic background. These results also suggest that roscovitine may be a selective and effective chemotherapeutic agent against cervical carcinoma. 2. Materials and Methods Roscovitine was purchased from Sigma-Aldrich (CAS: 186692466, USA). C33A, HCE-1, HeLa, and SiHa cell lines were purchased

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