An anthelmintic and anticancer agent
Pyrvinium is an anthelmintic and anticancer agent.1,2 Dietary administration of pyrvinium reduces worm burden in mouse models of N. dubius, S. obvelata, or A. tetraptera infection (EC50s = 292, 4, and 17 ppm, respectively) but is lethal to mice at higher concentrations (LC50 = 600 ppm).1 Pyrvinium (1 μg/ml) induces cytotoxicity in PANC-1 cells cultured in glucose-deficient medium but not serum- or amino acid-deficient medium or complete medium.2 It reduces tumor growth in a PANC-1 mouse xenograft model when administered at a dose of 100 μg/mouse per day. Pyrvinium (10 nM) also binds to and activates casein kinase 1α (CK1α).3 It inhibits Wnt signaling (EC50 = ~10 nM in a reporter assay) in a CK1α-dependent manner. Formulations containing pyrvinium were previously used in the treatment of pinworm infections.
1.Brody, G.L., and Elward, T.E.Comparative activity of 29 known anthelmintics under standardized drug-diet and gavage medication regimens against four helminth species in miceJ. Parasitol.57(5)1068-1077(1971) 2.Esumi, H., Lu, J., Kurashima, Y., et al.Antitumor activity of pyrvinium pamoate, 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvationCancer Sci.95(8)685-690(2004) 3.Van Acker, H.H., Capsomidis, A., Smits, E.L., et al.CD56 in the immune system: More than a marker for cytotoxicity?Front. Immunol.8892(2017)
Cell experiment: | Pyrvinium pamoate is dissolved in DMSO at a concentration of 1 μM and is stocked in aliquots at -20°C. Cells (1×104) are suspended in 200 μL culture medium and then seeded into 96-well plates in quintuplicate overnight. Cells are treated with indicated concentrations of Pyrvinium pamoate (0-8,000 μM). After incubating for 3 days, CCK8 (10 μL) is added into each well and incubated at 37°C for 1 h. The absorbance is measured using a microplate reader at 450 nm[1]. |
Animal experiment: | Mice: NOD/SCID mice are housed under aseptic conditions in individually ventilated cages. For xenografting, 5×106 Pyrvinium pamoate-pretreated or untreated breast cancer cells (MDA-MB-231) are resuspended in a 1:1 mixture of culture medium and Matrigel and then transplanted into the fourth pair of mammary fat pads of mice (4-6-week-old). After injection, tumor size is measured by calipers each day and tumor growth is plotted. Upon reaching the endpoint, mice are sacrificed and tumors are harvested. All the tumors are formalin-fixed, and paraffin-embedded for hematoxylin and eosin and immunohistochemical staining[1]. |
参考文献: [1]. Xu L, et al. WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol. 2016 Mar;48(3):1175-86. | |
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