Diallyl trisulfide potentiates chemotherapeutic efficacy of doxorubicin in experimentally induced mammary carcinoma: Role of Notch signaling

The prevalence of breast cancer is remarkably increasing worldwide. Therefore, introduction of new approaches along with improvement of the existing ones in cancer treatment field is of great demand. The present study was designated to investigate the anti-proliferative role of Diallyl trisulfide (DATS) alone or in combination with Doxorubicin (Doxo) in Ehrlich solid carcinoma (ESC)-bearing mice. ESC was induced in female albino mice as an experimental model for breast cancer. The anti-tumorigenic effect of DATS was mediated by suppression of Notch signaling proteins (Notch 1, JAG 1 and HES 1), attenuation of tumor inflammation (NFκB, TNF-α, IL-6, IL-1β) and proliferation (cyclin D1, Ki67) and enhancement of apoptosis (caspase 3, p53). DATS and Doxo mono-treatments displayed opposing effect regarding expression of Notch signaling proteins and cyclin D1 gene expression. However, DATS and Doxo co-treatment markedly decreased tumor volume and weight, increased animals' survival rate, and attenuated Doxo-induced tumor inflammation. In parallel, microscopic investigation displayed that ESC tumor tissues from animals treated with DATS and/or DOX showed shrinkage of tumor lesions and wider zones of apoptosis. In conclusion, DATS acts via multiple molecular targets to elicit anti-proliferative activity. Combination of DATS with Doxo -which exhibit different mechanisms of action- might be a potential novel strategy to augment Doxo-antitumor effect.

Keywords: Apoptosis; Carcinoma; Diallyl trisulfide; Ehrlich; Notch; Solid.