Tephrosin attenuates breast cancer via the modulation of TRAP1/HIF-1α/SDHA expression: <i>in vitro</i> and <i>in vivo</i> approach

Abstract Objectives Breast cancer is the most commonly diagnosed malignancy among women worldwide. Our study explored the chemotherapeutic activity of tephrosin in breast cancer treatment. Methods The in vitro study has been performed on MCF-7 cell line through cell viability and flow cytometry assay. The toxicity study was conducted by acute and subacute toxicity study to determine LD50 and ED50 doses of tephrosin for further chemotherapeutic study. In in vivo assessment, the breast cancer has been induced in rat via the single i.v administration of 7,12-Dimethylbenz[a]anthracene (DMBA) with dose of 0.5 mg/100 g body weight in corn oil. Subsequently, the tephrosin treatment through oral route has been commenced in carcinogen-induced rats that sustained for 24 weeks. The immunohistochemistry, histopathology, cell proliferation study and apoptosis assay via TUNEL method have been performed to evaluate the restoration of normal cellular architecture of breast tissues through upregulation of succinate dehydrogenase subunit A (SDHA) expression. Results Our results showed that the treatment with tephrosin causes the downregulation of tumor necrosis factor receptor-associated protein 1 (TRAP1) expression in mitochondrial matrix and decreases the stabilization of succinate-dependent HIF-1α, leading to the upstream of SDHA protein levels in breast cancer tissues. Conclusions In conclusion, the progression of breast cancer has been attenuated by the initiation of apoptotic events and distortion of cellular proliferation, which is permissible for the development of a suitable molecular mechanistic pathway of tephrosin in breast cancer chemotherapy.