Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Abstract

Breast cancer (BC) is the most frequent cancer among women worldwide and is the leading cause of cancer-related deaths in women. Cancer cells with stem cell-like features and tumor-initiating potential contribute to drug resistance, tumor recurrence, and metastasis. To achieve better clinical outcomes, it is crucial to eradicate both bulk BC cells and breast cancer stem cells (BCSCs). Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis. There is increasing evidence that salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis. Therefore, salinomycin is a promising therapeutic drug for BC. In this review, we summarize established mechanisms by which salinomycin protects against BC and discuss its future clinical applications.

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

“…[ 80 ] demonstrated that salinomycin improved cell death receptors in CRC‐SCs by inhibiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a histone‐lysine N‐methyltransferase enzyme. Importantly, salinomycin has also been reported to target CSCs of various types of cancer, including melanoma [ 81 ], osteosarcoma [ 82 ], breast [ 83 ], liver [ 84 ], brain [ 85 ], ovarian [ 86 ], and oral cancers [ 87 ]. Salinomycin specifically eliminated epithelial CSCs [ 88 ].…”

BSA–MnO2–SAL multifunctional nanoparticle-mediated M1 macrophages polarization for glioblastoma therapy

“…The tumour growth inhibition mechanism of SAL mainly depends on apoptosis induction, necrosis efficacy, and tumour stem cell cytotoxicity, among other factors. 24–26 However, few studies have investigated the effects of SAL on the immune microenvironment and the underlying mechanism. Unlike previously reported findings, in this study, we found that the repolarization ability of SAL on M 2 macrophages was positively correlated with the drug concentration and that it had no obvious toxic effect on macrophages.…”

A Review of Twenty Years of Research on the Regulation of Signaling Pathways by Natural Products in Breast Cancer

“…Salinomycin (SAL) is a potent antibiotic used for the treatment of BC. It is derived from Streptomyces albus and was useful for inhibition, cell proliferation, and the suppression of tumor growth [ 135 ]. SAL also induced apoptosis and cell death in metastatic BC cells by promoting DNA damage and elevating ROS production.…”