Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR‑ABL‑positive CML cells

Zhang,Jing; Jin,Yanli; Pan,Jingxuan

doi:10.3892/mmr.2017.7685

Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR‑ABL‑positive CML cells

Authors:
- Jing Zhang
- Yanli Jin
- Jingxuan Pan
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Affiliations: Jinan University Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: October 2, 2017 https://doi.org/10.3892/mmr.2017.7685
Pages: 9217-9223

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Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the BCR‑ABL oncogene, which encodes a constitutively activated tyrosine kinase. Despite progress in controlling CML at the chronic phase by first and second generations of BCR‑ABL tyrosine kinase inhibitors (TKIs), effective drugs with good safety are not available for CML patients harboring T315I BCR‑ABL and those in advanced stages of CML. Therefore, there is an urgent requirement for the development of effective therapies against T315I BCR‑ABL. In the present study, it was demonstrated that pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration had potent inhibitory effects on growth and survival in CML cells with T315I BCR‑ABL. In addition, this agent was equally effective in inhibiting the Wnt/β‑catenin signaling in wild‑type and T315I BCR‑ABL CML cells. Thus, the clinical efficacy of pyrvinium pamoate in treating patients with CML bearing T315I BCR‑ABL should be further investigated.

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1	Rowley JD: Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 243:290–293. 1973. View Article : Google Scholar : PubMed/NCBI
2	McLaughlin J, Chianese E and Witte ON: In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the philadelphia chromosome. Proc Natl Acad Sci USA. 84:pp. 6558–6562. 1987; View Article : Google Scholar : PubMed/NCBI
3	Slupianek A, Falinski R, Znojek P, Stoklosa T, Flis S, Doneddu V, Pytel D, Synowiec E, Blasiak J, Bellacosa A and Skorski T: BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability. Leukemia. 27:629–634. 2013. View Article : Google Scholar : PubMed/NCBI
4	Kim SJ, Jung KH, Yan HH, Son MK, Fang Z, Ryu YL, Lee H, Lim JH, Suh JK, Kim J, et al: HS-543 induces apoptosis of Imatinib-resistant chronic myelogenous leukemia with T315I mutation. Oncotarget. 6:1507–1518. 2015. View Article : Google Scholar : PubMed/NCBI
5	Bu Q, Cui L, Li J, Du X, Zou W, Ding K and Pan J: SAHA and S116836, a novel tyrosine kinase inhibitor, synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells. Cancer Biol Ther. 15:951–962. 2014. View Article : Google Scholar : PubMed/NCBI
6	Senior M: FDA halts then allows sales of Ariad's leukemia medication. Nat Biotechnol. 32:9–11. 2014. View Article : Google Scholar : PubMed/NCBI
7	Jung RC: Treatment of intestinal parasitic disease. South Med J. 69:799–804. 1976. View Article : Google Scholar : PubMed/NCBI
8	Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F and Lisanti MP: Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease. Oncotarget. 6:4569–4584. 2015. View Article : Google Scholar : PubMed/NCBI
9	Xu W, Lacerda L, Debeb BG, Atkinson RL, Solley TN, Li L, Orton D, McMurray JS, Hang BI, Lee E, et al: The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer. PLoS One. 8:e715082013. View Article : Google Scholar : PubMed/NCBI
10	Deng L, Lei Y, Liu R, Li J, Yuan K, Li Y, Chen Y, Liu Y, Lu Y, Edwards CK III, et al: Pyrvinium targets autophagy addiction to promote cancer cell death. Cell Death Dis. 4:e6142013. View Article : Google Scholar : PubMed/NCBI
11	Harada Y, Ishii I, Hatake K and Kasahara T: Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3. Cancer Lett. 319:83–88. 2012. View Article : Google Scholar : PubMed/NCBI
12	Yu DH, Macdonald J, Liu G, Lee AS, Ly M, Davis T, Ke N, Zhou D, Wong-Staal F and Li QX: Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy. PLoS One. 3:e39512008. View Article : Google Scholar : PubMed/NCBI
13	Thorne CA, Hanson AJ, Schneider J, Tahinci E, Orton D, Cselenyi CS, Jernigan KK, Meyers KC, Hang BI, Waterson AG, et al: Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α. Nat Chem Biol. 6:829–836. 2010. View Article : Google Scholar : PubMed/NCBI
14	Li B, Fei DL, Flaveny CA, Dahmane N, Baubet V, Wang Z, Bai F, Pei XH, Rodriguez-Blanco J, Hang B, et al: Pyrvinium attenuates Hedgehog signaling downstream of smoothened. Cancer Res. 74:4811–4821. 2014. View Article : Google Scholar : PubMed/NCBI
15	Li B, Flaveny CA, Giambelli C, Fei DL, Han L, Hang BI, Bai F, Pei XH, Nose V, Burlingame O, et al: Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. PLoS One. 9:e1019692014. View Article : Google Scholar : PubMed/NCBI
16	Xiang W, Cheong JK, Ang SH, Teo B, Xu P, Asari K, Sun WT, Than H, Bunte RM, Virshup DM and Chuah C: Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration. Oncotarget. 6:33769–33780. 2015. View Article : Google Scholar : PubMed/NCBI
17	Zhang H, Trachootham D, Lu W, Carew J, Giles FJ, Keating MJ, Arlinghaus RB and Huang P: Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism. Leukemia. 22:1191–1199. 2008. View Article : Google Scholar : PubMed/NCBI
18	Lu Z, Jin Y, Qiu L, Lai Y and Pan J: Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation. Cancer Lett. 290:182–191. 2010. View Article : Google Scholar : PubMed/NCBI
19	Qiu L, Wang XD, Yu BH, Lu RZ, Ge F, Wang XL, Chen LJ, Han BH, Zhan ZM, Zhang BL and Ma J: Effect of a novel tyrosine kinase inhibitor HHGV678 on growth inhibition of Bcr-Abl wild type and IM-resistant cell lines in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 16:1039–1043. 2008.(In Chinese). PubMed/NCBI
20	Pan J, Quintas-Cardama A, Kantarjian HM, Akin C, Manshouri T, Lamb P, Cortes JE, Tefferi A, Giles FJ and Verstovsek S: EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation. Blood. 109:315–322. 2007. View Article : Google Scholar : PubMed/NCBI
21	Jin Y, Chen Q, Shi X, Lu Z, Cheng C, Lai Y, Zheng Q and Pan J: Activity of triptolide against human mast cells harboring the kinase domain mutant KIT. Cancer Sci. 100:1335–1343. 2009. View Article : Google Scholar : PubMed/NCBI
22	Jin Y, Lu Z, Ding K, Li J, Du X, Chen C, Sun X, Wu Y, Zhou J and Pan J: Antineoplastic mechanisms of niclosamide in acute myelogenous leukemia stem cells: Inactivation of the NF-kappaB pathway and generation of reactive oxygen species. Cancer Res. 70:2516–2527. 2010. View Article : Google Scholar : PubMed/NCBI
23	Lu B, Li J, Pan J, Huang B, Liu J and Zheng D: Everolimus enhances the cytotoxicity of bendamustine in multiple myeloma cells through a network of pro-apoptotic and cell-cycle-progression regulatory proteins. Acta Biochim Biophys Sin (Shanghai). 45:683–691. 2013. View Article : Google Scholar : PubMed/NCBI
24	Shi X, Jin Y, Cheng C, Zhang H, Zou W, Zheng Q, Lu Z, Chen Q, Lai Y and Pan J: Triptolide inhibits Bcr-Abl transcription and induces apoptosis in STI571-resistant chronic myelogenous leukemia cells harboring T315I mutation. Clin Cancer Res. 15:1686–1697. 2009. View Article : Google Scholar : PubMed/NCBI
25	Pan J, Xu G and Yeung SC: Cytochrome c release is upstream to activation of caspase-9, caspase-8, and caspase-3 in the enhanced apoptosis of anaplastic thyroid cancer cells induced by manumycin and paclitaxel. J Clin Endocrinol Metab. 86:4731–4740. 2001. View Article : Google Scholar : PubMed/NCBI
26	Blonska M, Shambharkar PB, Kobayashi M, Zhang D, Sakurai H, Su B and Lin X: TAK1 is recruited to the tumor necrosis factor-alpha (TNF-alpha) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-kappaB activation. J Biol Chem. 280:43056–43063. 2005. View Article : Google Scholar : PubMed/NCBI
27	Zhang X, Lou Y, Zheng X, Wang H, Sun J, Dong Q and Han B: Wnt blockers inhibit the proliferation of lung cancer stem cells. Drug Des Devel Ther. 9:2399–2407. 2015.PubMed/NCBI
28	Beck JW, Saavedra D, Antell GJ and Tejeiro B: The treatment of pinworm infections in humans (enterobiasis) with pyrvinium chloride and pyrvinium pamoate. Am J Trop Med Hyg. 8:349–352. 1959. View Article : Google Scholar : PubMed/NCBI
29	Liu MD, Xiong SJ, Tan F and Liu Y: Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression. Acta Pharmacol Sin. 37:687–697. 2016. View Article : Google Scholar : PubMed/NCBI
30	Basu D, Reyes-Mugica M and Rebbaa A: Role of the beta catenin destruction complex in mediating chemotherapy-induced senescence-associated secretory phenotype. PLoS One. 7:e521882012. View Article : Google Scholar : PubMed/NCBI