Oral Administration of Withaferin A Increases Infiltration of CD4+ Helper T Cells in a Mouse Model of Mammary Tumor.

Withaferin A (WA) is a small molecule present in Ashwagandha plant that prevents breast cancer progression in mice and rats. The mechanisms underlying breast cancer prevention by WA are not fully understood. Herein, we report effects of WA treatment on an immune landscape in C3(1)-TAg transgenic mice, which develop basal-like breast cancer. Oral administration of 12 mg/kg body weight of WA decreased the wet tumor weight by about 43%. Weight loss or any other adverse effects (e.g., impaired movement, hunched back, ruffled fur, etc.) were not observed. Tumors and splenocytes from WA-treated mice exhibited the increased proportion of CD4+ helper T cells when compared to control mice. The proportion of CD8α+ T cells and natural killer cells was not affected by WA treatment in either mammary tumor or splenocytes. Similarly, the proportions of lymphoid dendritic cells, myeloid dendritic cells, M2 macrophages, regulatory T cells, and myeloid-derived suppressor cells were comparable in mammary tumors and splenocytes of both control and WA-treated mice. Unlike the C3(1)-TAg mouse model, WA administration failed to increase the proportion of CD4+ T cells in mammary tumors of rats. The present study indicates that even though WA treatment increases the proportion of helper T cells in mammary tumors and spleen, attenuation of immune evasion may have a minimal role in its breast cancer prevention at least in rodent models of basal-like [C3(1)-TAg model] and luminal-type (rat model) breast cancer.