Tetraarsenic O xide-mediated Apoptosis in a C ervical Cancer Cell Line, SiHa
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Abstract
Purpose: Diarsenic oxide, As2O3, has been reported to be effective in treating acute leukemia, and induce apoptosis in many tumor cells. In this study, the ability of a novel arsenical compound, As4O6 (tetraarsenic oxide), along with As2O3, for its ability to induce cell growth inhibition, as well as apoptosis, in human cervical cancer cells, SiHa cells, were evaluated in vitro. Materials and Methods: To examine the levels of apoptosis, SiHa cells were given two sensitive doses, 0.5 and 1μM, of arsenical compounds, and a DNA fragmentation assay and FACS analysis were then conducted. In addition, a W estern blotting assay was performed to identify target m olecules for apoptosis. Results: Both As2O3 and As4O6 induced dosedependent inhibition of SiHa cell proliferation. In particular, As4O6 was m ore effective at suppressing SiHa cell growth than As2O3. In parallel with the inhibition of cell proliferation, As4O6 caused a significantly greater increase in the sub-G1 cell population than As2O3, as determined by propidium iodide DNA staining. This was confirmed by a DNA fragmentation assay and annexin V staining. The W estern blotting analysis also showed that the expression of proliferating cell nuclear antigen (PCNA) was suppressed to a significantly greater extent by As4O6 than As2O3 at a dose of 0.5μM. However, the apoptosis-related protein, Bax, was expressed to a significantly greater extent due to As4O6 than As2O3. Conclusion: Taken together, these findings suggest that a novel arsenic compound, As4O6, possesses more potent anti-proliferative effects on human cervical cancer cells, with the induction of apoptosis also, at least via the activation of Bax protein in vitro.
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