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

揭示紫杉叶素钌-对蒎烯复合物在乳腺癌中的化疗潜力:体外和体内对 AhR 信号通路的洞察

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作者:Abhijit Das, Barshana Bhattacharya, Sakuntala Gayen, Souvik Roy

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.

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.

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

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