Low-dose salinomycin inhibits breast cancer metastasis by repolarizing tumor hijacked macrophages toward the M1 phenotype

Shen, Huan; Sun, Changquan Calvin; Kang, Lichun; Tan, Xiaoyue; Shi, Peng; Wang, Lingyu; Liu, Ergang; Gong, Junbo

doi:10.1016/j.ejps.2020.105629

Cited by 15 publications

(15 citation statements)

References 28 publications

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“…First, at insufficient concentrations for direct antitumor activity, it could effectively stimulate M1 type macrophages and limit tumor growth and metastasis. In a previous study, the intratumoral injection of salinomycin increased the proportion of CD86 cells and decreased CD206 cells in transplant 4T1 tumors, thereby preventing tumor growth and pulmonary metastasis ( 62 ). Second, salinomycin could potently reverse tumor immune tolerance via the repression of IDO1 enzymatic activity.…”

Section: Multiple Functions Of Salinomycin In Bcmentioning

confidence: 95%

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

et al. 2021

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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.

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Section: Multiple Functions Of Salinomycin In Bcmentioning

confidence: 95%

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

et al. 2021

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“…Tumor-associated macrophages (TAMs) were obtained by incubating RAW246.7 macrophages with PC3 cells or si-MCT4-PC3 cells (PC3-TAM or si-MCT4-PC3-TAM). 30 We developed a co-culture model by seeding RAW246.7 macrophages (4×10 4 /well) in the lower chambers of the transwell plate with PC3 cells (1×10 4 /well) in the upper chambers. After co-culturing for 84 hours, RAW246.7 macrophages were collected and mRNA analysis was performed by real-time quantitative PCR.…”

Section: Methodsmentioning

confidence: 99%

“…Tumor-associated macrophages (TAMs) were obtained by incubating RAW246.7 macrophages with PC3 cells or si-MCT4-PC3 cells (PC3-TAM or si-MCT4-PC3-TAM). 30 We (dilution 1:100; Abcam, UK), ENO2 (dilution 1:300; Servicebio, Wuhan, China), and M2 macrophage marker CD163 (dilution 1:100; Servicebio, Wuhan, China) were used to detect protein expression at 4°C overnight, which was followed by incubation with HRP-conjugated secondary antibodies for 1 h at 37°C. The 3ʹdiaminobenzidine kit (DAB; Dako Corporation, Carpinteria, CA, USA) was used for immune complex visualization.…”

Section: Pc3 and Raw2647 Coculturedmentioning

confidence: 99%

Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer

Xie¹,

Guo²,

Zhang³

et al. 2021

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Purpose: Prostate cancer is the most common malignant urinary tumor among men. Treatments are currently unsatisfactory for advanced prostate cancer. Cancer biology remains the basis for developing new antitumor drugs. Therefore, it is crucial to study the metabolic reprogramming, immune microenvironment, and immune evasion of tumors. This study aimed to clarify the relationship between tumor glycolysis and immune function in prostate cancer. Materials and Methods: We downloaded the gene expression matrix and clinical data of prostate cancer from The Cancer Genome Atlas. We studied the expression profiles and prognostic significance of glycolysis-related genes and used CIBERSORT to identify the proportion of tumor-infiltrating immune cells. Through differential gene expression analysis, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis, and correlation analysis, we further explored the relationship between glycolytic activity and immune function. We also performed immunohistochemistry, Western blot and RT-qPCR experiments using human prostate cancer tissue and cell lines to verify the expression of some glycolytic genes, macrophage infiltration and polarization. Results: Among glycolysis-related genes, the expression of SLC16A3 in prostate cancer tissues was lower than that in normal tissues, but its high expression was associated with poor prognosis. In the high SLC16A3 expression group, several glycolysis-related genes also showed high expression, which was confirmed by immunohistochemistry experiments and Western blot. In high-glycolysis group, the expression of immune-related genes and the interleukin-17 (IL-17) signaling pathway were upregulated. CD8 + T cells, regulatory T cells, macrophages, and other immune cells were highly enriched. Among them, M2 macrophage infiltration was associated with poor prognosis. Conclusion:The enhanced glycolytic activity of prostate cancer may contribute to the formation of a pro-tumor immune microenvironment. The IL-17 signaling pathway may play an important mediating role in the interaction between tumor glycolysis and immune function.

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“…Studies have shown that SAL has the ability to repolarize M 2 macrophages in breast cancer, but its efficiency in GBM is unknown. 15 Furthermore, because of the presence of the blood–brain barrier (BBB), traditional chemotherapy has a limited effect and has incurred high recurrence rates in patients with GBM; therefore, improving the BBB penetration ability of drugs is important for the treatment of GBM. In addition, SAL exhibits similar limitations in chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Owing to its poor water solubility and low BBB penetration efficiency, the therapeutic effect of SAL on glioma is relatively limited. 15,16 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Low-dose salinomycin inhibits breast cancer metastasis by repolarizing tumor hijacked macrophages toward the M1 phenotype

Cited by 15 publications

References 28 publications

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer

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

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Low-dose salinomycin inhibits breast cancer metastasis by repolarizing tumor hijacked macrophages toward the M1 phenotype

Cited by 15 publications

References 28 publications

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Comprehensive Analysis of the Relationship Between Metabolic Reprogramming and Immune Function in Prostate Cancer

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

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