Low-Dose Salinomycin Alters Mitochondrial Function and Reprograms Global Metabolism in Burkitt Lymphoma

TL;DR

Low-dose salinomycin harms Burkitt lymphoma cells by disrupting mitochondria and changing their metabolism, suggesting it could help in cancer treatment.

Contribution

The study reveals that low-dose salinomycin reprograms cancer cell metabolism and induces oxidative stress in Burkitt lymphoma.

Findings

Salinomycin disrupts mitochondrial membrane potential and induces oxidative stress in Burkitt lymphoma cells.

Salinomycin shifts cellular metabolism from mitochondrial respiration to aerobic glycolysis.

Metabolomic analysis shows salinomycin causes arginine depletion in cancer cells.

Abstract

Salinomycin (SAL), originally identified for its potent antibacterial properties, has recently garnered attention for its remarkable activity against a variety of cancer types. Beyond its direct cytotoxic effects on cancer cells, SAL can also enhance the efficacy of anti-CD20 immunotherapy in B-cell malignancies, both in vitro and in vivo. Despite these promising findings, the precise molecular mechanisms underlying SAL’s anticancer action remain poorly understood. Here, we demonstrate that even at low concentrations (0.25–0.5 mM), SAL disrupts mitochondrial membrane potential and induces oxidative stress in Burkitt lymphoma. Further investigations uncovered that SAL shifts cellular metabolism from mitochondrial respiration to aerobic glycolysis. Additionally, metabolomic profiling identified SAL-induced arginine depletion as a key metabolic alteration. These findings provide new insights into SAL’s multifaceted mechanisms of action and support its potential as an adjunctive therapy in cancer treatment.

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