Sodium arsenite and dimethylarsenic acid induces apoptosis in OC3 oral cavity cancer cells

Although arsenic is an environmental toxicant, arsenic trioxide (ATO) is used to treat acute promyelocytic leukemia (APL) with anticancer effects. Studies have demonstrated oral cancer is in the top 10 cancers in Taiwan. High rate of oral cancers is linked to various behaviors, such as excessive alcohol consumption and tobacco use. Similarly, betel chewing is a strong risk factor in oral cancer. In the present study, oral squamous carcinoma OC3 cells were investigated with the treatments of sodium arsenite (NaAsO(2)) and dimethylarsenic acid (DMA), respectively, to examine if arsenic compounds have anti-cancer efforts. It was found that 1 µM NaAsO(2) and 1 mM DMA for 24 h induced rounded contours with membrane blebbing phenomena in OC3 cells, revealing cell apoptotic characteristics. In addition, NaAsO(2) (10–100 µM) and DMA (1–100 mM) significantly decreased OC3 cell survival. In cell cycle regulation detected by flow cytometry, NaAsO(2) and DMA significantly augmented percentage of subG(1) and G(2)/M phases in OC3 cells, respectively. Annexin V/PI double staining assay was further used to confirm NaAsO(2) and DMA did induce OC3 cell apoptosis. In mechanism investigation, western blotting assay was applied and the results showed that NaAsO(2) and DMA significantly induced phosphorylation of JNK, ERK1/2 and p38 and then the cleavages of caspase-8, −9, −3 and poly ADP-ribose polymerase (PARP) in OC3 cells, dynamically. In conclusion, NaAsO(2) and DMA activated MAPK pathways and then apoptotic pathways to induce OC3 oral cancer cell apoptosis.