Abstract Triple-negative and hormone receptor-negative breast cancers remain clinically challenging due to their aggressive nature and resistance to targeted therapies. This study investigated the chemopreventive potential of Pleurotus ostreatus ethanolic extract (PoEE), a natural bioactive compound, compared with vincristine, a conventional anticancer drug, in a chemically induced breast cancer model. Female Sprague-Dawley rats (n=48) were divided into eight groups, receiving either olive oil (control), DMBA-NMU carcinogens (80 mg/kg-10mg/kg), PoEE (600 mg/kg), vincristine (0.0005 mg/kg), or various combinations thereof. After 25 weeks of treatment, mammary tissues were subjected to histological and immunohistochemical analyses targeting key molecular markers involved in oncogenesis, apoptosis, inflammation, and DNA repair. Quantitative data were analyzed using ImageJ and GraphPad Prism. DMBA-NMU administration significantly upregulated pro-proliferative and oncogenic markers such as TERT (+24.45 fold), c-Myc (+7.37 fold), BCl-2 (+8.65 fold), and NFκB (+5.44 fold), while downregulating tumor suppressors including p53 (−93.33%), PTEN (−81.24%), and FOXO (−95.83%). PoEE markedly reversed these effects, achieving superior or comparable efficacy to vincristine across most markers. Notably, PoEE alone enhanced expression of BRCA1 (+4.83 fold) and BRCA2 (+2.17 fold), promoted pro-apoptotic proteins such as BAX (+1.74 fold) and Cyt-C (+69.07%), and suppressed anti-apoptotic BCl-2 by 87.04%. Vincristine showed weaker modulation of repair and apoptotic genes but synergized with PoEE to enhance BRCA1 (+8.66 fold), Cyt-C (+1.22 fold), and Caspase-3 (+3.89 fold) expression. Cell cycle arrest markers such as p27 and GSK3β were strongly upregulated in PoEE-treated groups, and DNA repair regulators BRCA1/2 exhibited additive or synergistic increases when PoEE was combined with vincristine. Inflammatory biomarker NFκB was suppressed by PoEE alone (−87.21%), but paradoxically upregulated when combined with vincristine (+33.72%), suggesting treatment-specific feedback effects. Similarly, the dual treatment attenuated PTEN and Caspase-8 levels, indicating potential antagonism. Collectively, PoEE demonstrated robust multi-target modulation of the PI3K/Akt downstream signaling pathway and associated oncogenic cascades, restoring tumor suppressor activity, promoting apoptosis, and enhancing DNA repair fidelity. These findings underscore PoEE’s promise as a low-toxicity therapeutic and adjuvant candidate for managing aggressive breast cancer subtypes, especially in contexts where conventional therapies are limited or ineffective. Citation Format: Magdalene Eno. Effiong, Shalom Nwodo. Chinedu, Israel Sunmola. Afolabi, Nwamaka Cynthia. Ikeji, Ebenezer Olatunde. Farombi. Pleurotus ostreatus ethanolic extract suppresses cell proliferation and restores apoptotic and DNA repair pathways in DMBA-NMU-induced breast cancer in female Sprague Dawley rats abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C053.
Effiong et al. (Thu,) studied this question.