Unraveling the chemotherapeutic potential of taxifolin ruthenium-p-cymene complex in breast carcinoma: Insights into AhR signaling pathway in vitro and in vivo

Abstract

Background: Mammary carcinoma is the most frequently diagnosed form of carcinoma in women worldwide. The organometallic compounds showed a prospective anticancer activity. This research explored the anticancer efficacy of taxifolin ruthenium-p-cymene counter to breast cancer. Methods: The anticancer efficacy of the novel organometallic compound was investigated via various in vitro and in vivo techniques using breast cancer cell lines and breast cancer model of rat. Results: Target proteins were identified via pharmacophore analysis, which revealed a high binding affinity towards AhR, EGFR, and β-catenin. The compound induced apoptotic events and prevented cancer cell colony formation. Furthermore, decreased expression of AhR, EGFR, and N-cadherin inhibited cancer cell growth, migration, and proliferation. The compound provoked the cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and inaugurated the caspase-3 dependent apoptotic events. The in-vivo experimentation displayed the fruitful restoration of breast tissue since the complex treatment in DMBA persuaded breast carcinoma in rat. Moreover, the upstream of p53 and caspase-3 expression along with substantially downstream of vimentin, β-catenin, m-TOR and Akt expression. Conclusions: In conclusion, the compound repressed the cancerous cellular viability, migration, and EMT via modulating the AhR/EGFR/ PI3K transduction pathway and the expression of EMT biomarkers such as N-cadherin, E-cadherin, thus eventually revoked the EMT facilitated metastasis of malignant cells.

Keywords

• Ruthenium-p-cymene
• Taxifolin
• Epithelial-to-mesenchymal transition
• Breast carcinoma
• AhR pathway