Monensin is a polyether ionophore antibiotic with anticancer activity. Monensin selectively binds monovalent cations such as Na⁺ and K⁺ and mediates Na⁺/H⁺ exchange. Monensin inhibits Gram-positive bacteria and coccidia by disrupting intracellular ion gradients, osmotic pressure and pH homeostasis. Monensin interferes with Golgi protein transport and inhibits autophagic flux. Monensin can be used in research related to bacterial infections, coccidiosis, viral infections, and cancer[1-4].
In vitro, Panc-1 and MiaPaCa-2 cells were treated with 0.5-8µM Monensin for 48-72 hours. Monensin inhibited cell proliferation and migration, arrested the cell cycle at the sub-G1 phase and decreased the S-phase population, and increased the proportion of apoptotic cells[5]. UOK146 cells were treated with 5-25µM Monensin for 24 hours. Monensin induced cell death, caused vacuolar morphological changes, and decreased mitochondrial membrane potential[6]. H1299 cells were treated with 500nM Monensin for 0-24 hours. Monensin reduced GOLIM4 protein levels in the Golgi apparatus and inhibited cell migration and invasion[7].
In vivo, BALB/c mice were intranasally sensitized with 10μg house dust Mite extract (HDM) twice weekly for 6 weeks. Monensin was administered via i.p. (1mg/kg) or i.n. (0.25-1mg/kg) 30min prior to each sensitization. Monensin reduced total cell, eosinophil and lymphocyte counts in bronchoalveolar lavage fluid, decreased lung inflammation scores, and alleviated lung tissue inflammation[8]. 4T1-Luc2 tumor xenograft BALB/c mice were intraperitoneally injected with 8mg/kg Monensin daily for 10 consecutive days. Monensin increased intracellular Na⁺ levels in tumor cells, reduced tumor volume, and induced extensive tumor necrosis[9]. Apc+/Min mice were orally gavaged with 10mg/kg Monensin daily for 6 consecutive weeks. Monensin reduced average intestinal tumor area and total tumor area per animal, increased the number of apoptotic cells and p21-positive cells on the tumor surface, and did not change tumor number[10].
References:
[1] Potter EL, VanDuyn RL, Cooley CO. Monensin toxicity in cattle. J Anim Sci. 1984 Jun;58(6):1499-511.
[2] Zeng C, Long M, Lu Y. Monensin synergizes with chemotherapy in uveal melanoma through suppressing RhoA. Immunopharmacol Immunotoxicol. 2023 Feb;45(1):35-42.
[3] Li Y, Sun Q, Chen S, et al. Monensin Inhibits Anaplastic Thyroid Cancer via Disrupting Mitochondrial Respiration and AMPK/mTOR Signaling. Anticancer Agents Med Chem. 2022;22(14):2539-2547.
[4] Donoho AL. Biochemical studies on the fate of monensin in animals and in the environment. J Anim Sci. 1984 Jun;58(6):1528-39.
[5] Wang X, Wu X, Zhang Z, et al. Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway. Scientific Reports. 2018 Dec 17;8:17914.
[6] Verma SP, Das P. Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line. In Vitro Cellular & Developmental Biology - Animal. 2018 Oct;54(8):736-42.
[7] Tan X, Cardin DL, Wang S, et al. Monensin suppresses EMT-driven cancer cell motility by inducing Golgi pH-dependent exocytosis of GOLIM4. PNAS. 2025 Jul 9;122(28):e2501347122.
[8] Allam VSRR, Akula S, Waern I, et al. Monensin suppresses multiple features of house dust mite-induced experimental asthma in mice. Inflammation. 2025;48:806-19.
[9] Fiorilla S, Tasso F, Clemente N, et al. Monensin inhibits triple-negative breast cancer in mice by a Na+-dependent cytotoxic action unrelated to cytostatic effects. Cells. 2025 Jan 25;14(3):185.
[10] Tumova L, Pombinho AR, Vojtechova M, et al. Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice. Molecular Cancer Therapeutics. 2014 Apr;13(4):812-22.