The incidence of testicular cancer is increasing worldwide. Leydig cell tumors represent one type of sex cord-stromal testis malignancy, which tend to respond unfavorably to chemotherapies. Identifying more efficient treatment strategies is therefore crucial for patients. The present study aimed to investigate the apoptotic effects of arsenic compounds and their underlying mechanisms. The results indicated that sodium arsenite and dimethylarsenic acid induced apoptosis of the murine Leydig tumor cell line, MA-10. These apoptotic effects were characterized morphologically by membrane blebbing and cell detachment assays, biochemically using a cell viability assay, and cytologically by flow cytometry analysis. Western blotting demonstrated that caspases-3,-8 and-9, and poly(ADP-ribose) polymerase protein levels were increased compared with untreated MA-10 cells; however, the caspase inhibitor, Z-VAD-fmk, reversed these effects. In conclusion, the present study has shown that sodium arsenite and dimethylarsenic acid may activate the intrinsic and extrinsic caspase pathways, and induce MA-10 cell apoptosis. These results suggest that sodium arsenite and dimethylarsenic acid may represent novel approaches to treat clinically unmanageable forms of testicular cancer.

Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA‐10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA‐10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA‐10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA‐10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA‐10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA‐10 cell apoptosis.