Zdanowicz Aleksandra, Ilchenko Oleksandr, Ciechanowicz Andrzej, Chi Haoyu, Struga Marta, Pyrzynska Beata
Department of Biochemistry, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland.
Doctoral School, Medical University of Warsaw, Zwirki i Wigury 81 Str., 02-091 Warsaw, Poland.
Int J Mol Sci. 2025 May 27;26(11):5125. doi: 10.3390/ijms26115125.
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 and . 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.
沙利霉素（SAL）最初因其强大的抗菌特性而被发现，最近因其对多种癌症类型具有显著活性而受到关注。除了对癌细胞的直接细胞毒性作用外，SAL还可以增强抗CD20免疫疗法在B细胞恶性肿瘤中的疗效。尽管有这些有前景的发现，但SAL抗癌作用的精确分子机制仍知之甚少。在这里，我们证明即使在低浓度（0.25 - 0.5 mM）下，SAL也会破坏伯基特淋巴瘤中的线粒体膜电位并诱导氧化应激。进一步的研究发现，SAL将细胞代谢从线粒体呼吸转变为有氧糖酵解。此外，代谢组学分析确定SAL诱导的精氨酸消耗是关键的代谢改变。这些发现为SAL多方面的作用机制提供了新的见解，并支持其作为癌症治疗辅助疗法的潜力。
