Background: Breast cancer remains a leading cause of mortality among women worldwide, with increasing resistance to chemotherapy and radiotherapy. Overexpression of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) and its downstream effectors, such as NQO1 and HO-1, contributes to cancer progression and therapy resistance. The present study explores the antitumor potential of the NRF2-modulating fraction of Anacyclus pyrethrum (AP) using an EAC (Ehrlich Ascites Carcinoma) solid tumor model.
Objective: To evaluate the in vitro and in vivo efficacy of Anacyclus pyrethrum ethanolic extract (EEAP) in inhibiting tumor progression via NRF2 pathway modulation.
Methods: Ethanolic extract of Anacyclus pyrethrum was prepared using Soxhlet extraction. In vitro cytotoxicity was assessed using SRB assays on breast cancer cell lines, and in vivo antitumor activity was evaluated in EAC-induced Swiss albino mice. Tumor volume reduction, histological changes, and NRF2-associated signaling markers were assessed.
Results: The ethanolic extract of Anacyclus pyrethrum demonstrated significant in vitro cytotoxicity, with maximum inhibition observed at a concentration of 31.25 µg/mL after 72 hours. In vivo, tumor volume reduction and enhanced necrosis were observed in treated groups. Histopathological analysis showed substantial cell death in tumor tissues of mice treated with EEAP. NRF2 signaling inhibition, confirmed by NQO1 assays, revealed a dose-dependent response to EEAP, suggesting downregulation of NRF2-mediated pathways.
Conclusion: This study highlights the potential of Anacyclus pyrethrum as a rich source of phytochemicals with significant antitumor properties. The extract effectively inhibits NRF2-mediated tumor progression, supporting its future development as a therapeutic agent for breast cancer management.
Keywords: Breast cancer, Anacyclus pyrethrum, NRF2 modulation, EAC tumor model, Anticancer phytochemicals
