Monensin

Monensin(protein transport inhibitor) is an ionophore, which can destroy the Golgi apparatus and inhibit intracellular protein transport. Monensin is commonly used as a protein transport inhibitor.

Monensin is also often used to inhibit the secretion of secreted proteins such as cytokines, and to enhance the staining of secreted proteins by inhibiting secretion during immunostaining. As an ionophore, Monensin can selectively bind monovalent cations into Li+,Na+,K+,Rb+,Ag+ and Ti+, and transport these cations to the cell membrane^[3,4].

Monensin could significantly inhibit the proliferation of A549 cells in vitro.Monensin induced G phase arrest in A549 cells, and the proteins related to G phase arrest were changed.Monensin can promote autophagy in A549 cells.Monensin can induce apoptosis in A549 cells^[1]. Monensin is a potent inducer of oxidative stress and inhibitor of androgen signaling leading to apoptosis in prostate cancer cells. Monensin as a potential well-tolerated, in vivo compatible drug with strong proapoptotic effects in prostate cancer cells, and synergistic effects with antiandrogens^[5].Nanomolar concentrations of Monensin inhibit early stages of capillary network formation in glioblastoma endothelial cells Monensin inhibits multiple endothelial events, including migration, growth and survival, without affecting adhesion to Matrigel by inhibiting VEGFR and EGFR Mediated signaling pathways act on endothelial cells^[2]. Monensin can inhibit the proliferation and migration and activate apoptosis of breast cancer cells via downregulating the expression of UBA2^[7].

The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats^[6].

References:
[1]:Guo RT. Preliminary study on the mechanism of monensin action on A549 cells.2018. Qufu Normal University,MA Thesis.
[2]: Wan W, Zhang X, et,al. Monensin inhibits glioblastoma angiogenesis via targeting multiple growth factor receptor signaling. Biochem Biophys Res Commun. 2020 Sep 17;530(2):479-484. doi: 10.1016/j.bbrc.2020.05.057. Epub 2020 Jun 25. PMID: 32595038.
[3]: Nachliel E, Finkelstein Y, et,al.The mechanism of monensin-mediated cation exchange based on real time measurements. Biochim Biophys Acta. 1996 Dec 4;1285(2):131-45. doi: 10.1016/s0005-2736(96)00149-6. PMID: 8972697.
[4]: Huczy¨½ski A, Klejborowska G, et,al. Anti-proliferative activity of Monensin and its tertiary amide derivatives. Bioorg Med Chem Lett. 2015 Oct 15;25(20):4539-43. doi: 10.1016/j.bmcl.2015.08.067. Epub 2015 Aug 28. PMID: 26338363.
[5]: Ketola K, Vainio P, et,al. Monensin is a potent inducer of oxidative stress and inhibitor of androgen signaling leading to apoptosis in prostate cancer cells. Mol Cancer Ther. 2010 Dec;9(12):3175-85. doi: 10.1158/1535-7163.MCT-10-0368. PMID: 21159605.
[6]: Singh M, Kalla NR, et,al. Testicular effects of monensin, a golgi interfering agent in male rats. Drug Chem Toxicol. 2014 Oct;37(4):384-90. doi: 10.3109/01480545.2013.866955. Epub 2013 Dec 16. PMID: 24341700.
[7]: Gu J, Huang L, et,al. Monensin inhibits proliferation, migration, and promotes apoptosis of breast cancer cells via downregulating UBA2. Drug Dev Res. 2020 Sep;81(6):745-753. doi: 10.1002/ddr.21683. Epub 2020 May 27. PMID: 32462716.