Soy\'s secret weapon: Genistein\'s fight against triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment options. Genistein a natural isoflavone found in soybeans and legumes is a plant-based compound with anticancer properties that has been shown to be promising for TNBC treatment in preclinical studies. This review examines genistein’s potential as a therapeutic agent against TNBC. In vitro studies reveal its capacity to inhibit cell growth, induce apoptosis, and suppress TNBC metastasis. In vivo, genistein suppresses tumor growth and extends survival in TNBC mice. It targets key oncogenic pathways, including NF-κB, Akt, and PI3K. It has also been shown to regulate apoptosis-related gene expression, promote apoptosis, and activate the DNA damage response. Furthermore, Genistein demonstrated the ability to reactivate estrogen receptor expression in ERα-negative MDA-MB-231 xenograft mice, particularly when combined with the histone deacetylase inhibitor trichostatin A. This reactivation restored ER-dependent cellular sensitivity to tamoxifen and 17-estradiol. Combination therapy with genistein and other drugs or phytochemicals has shown to be particularly effective in preclinical studies. These findings suggest that Genistein holds promise as a potential therapeutic agent for TNBC by targeting key signaling pathways involved in cell proliferation, survival, and apoptosis, as well as modulating ER expression and enhancing sensitivity to existing therapies.