Plumbagin Inhibits Cadmium-Induced Interleukin-6/STAT3 Signaling in the Triple-Negative Breast Cancer Cell Line

Document Type : Research Articles

Authors

1 Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand.

2 Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand.

Abstract

Introduction: Plumbagin has been found to reduce proinflammatory cytokine expression in activated macrophages and carrageenan-induced paw edema. Cadmium triggers the release of interleukin-6 (IL-6), a key mediator of inflammation and carcinogenesis in many cell types. The effects of plumbagin on cadmium-induced inflammation in triple-negative breast cancer cells are unknown. Method: We investigated the effects of plumbagin on cadmium-induced IL-6 expression and signal transducer and activator of transcription 3 (STAT3) activation in MDA-MB-231, a triple-negative breast cancer cell line, using real-time PCR, ELISA, and Western blotting. Result: Non-cytotoxic concentrations of cadmium chloride at 1 and 10 μM upregulated the IL-6 mRNA expression after 3 h of exposure and increased the IL-6 release after 24 h. Plumbagin at 4 μM or more was toxic to cells after 24 h. Plumbagin at 1 μM co-treated with cadmium reduced the expression and secretion of IL-6. At 24-h post-exposure, plumbagin decreased the levels of phosphorylated STAT3 induced by cadmium. Conclusion: Plumbagin inhibits cadmium-induced IL-6/STAT3 signaling in a triple-negative breast cancer cell and further in vivo studies are required to elucidate the potential use of plumbagin on cancer progression.

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