Apoptosis-induced Cell Growth Inhibitory Effects of a Novel Compound, As4O6 in a Cervical Cancer Cell Line, SiHa in Vitro

다국어 초록 (Multilingual Abstract)

As2O3 has been reported to be effective for treating acute leukemia and induce apoptosis in many tumor cells. In this study, we evaluated the ability of a novel arsenical compound, As4O6, along with As2O3 to induce cell growth inhibition as well as apoptosis in human cervical cancer cells, SiHa cells in vitro. To examine the levels of apoptosis, SiHa cells were given two sensitive doses, 0.5 and 1μM of arsenical compounds, and then, DNA fragmentation assay and FACS analysis were conducted. In addition, Western blotting assay was done for the identification of target molecules for apoptosis. Both As2O3 and As4O6 caused dose-dependent inhibition of SiHa cell proliferation. In particular, As4O6 was more effective for suppressing SiHa cell growth, as compared to As2O3. In parallel with inhibition of cell proliferation, As4O6 caused an increase of the sub-G1 cell population significantly more than As2O3, as determined by propidium iodide DNA staining. This was confirmed by DNA fragmentation assay and annexin V staining. Western blotting analysis also showed that the proliferating cell nuclear antigen (PCNA) expression was suppressed by As4O6 significantly more than As2O3, and that Bcl-XL with sequence homology to Bcl-2 was significantly suppressed by As4O6. However, apoptosis-related proteins, p21 and Bax, were expressed by As4O6 significantly more than As2O3. Taken together, these findings suggest that a novel arsenic compound, As4O6 possesses more potent anti-proliferative effects on human cervical cancer cells with induction of apoptosis at least through activation in p21 and Bax proteins in vitro. (Cancer Prev Res 11, 39-45, 2006)

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