Oxibendazole inhibits prostate cancer cell growth

Chen,Qiaoli; Li,Yuhua; Zhou,Xiaoyu; Li,Runsheng

doi:10.3892/ol.2017.7579

Oxibendazole inhibits prostate cancer cell growth

Authors:
- Qiaoli Chen
- Yuhua Li
- Xiaoyu Zhou
- Runsheng Li
View Affiliations

Affiliations: School of Pharmacy, Fudan University, Shanghai 201203, P.R. China, Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, P.R. China
Published online on: December 11, 2017 https://doi.org/10.3892/ol.2017.7579
Pages: 2218-2226
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Prostate cancer (PCa) is one of the most common malignancies among men and is the second leading cause of cancer‑associated mortality in the developed world. Androgen deprivation therapy (ADT) is the most common treatment for PCa. However, the majority of androgen‑sensitive PCa patients will eventually develop resistance to ADT and the disease will become androgen‑independent. There is, therefore, an immediate requirement to develop effective therapeutic techniques towards the treatment of recurrent PCa. Oxibendazole (OBZ) is an anthelmintic drug that has also shown promise in the treatment of malignancies. In the present study, the capability of OBZ to repress the growth of PCa cells was assessed in human androgen‑independent PCa 22Rv1 and PC‑3 cell lines. The growth of the 22Rv1 and PC‑3 cell lines, as assessed with a trypan blue exclusion assay, was markedly inhibited by OBZ treatment in vitro, with half‑maximal inhibitory concentration values of 0.25 and 0.64 µM, respectively. The mean size of 22Rv1 tumors in nude mice treated with OBZ (25 mg/kg/day) was 47.96% smaller than that of the control mice. Treatment with OBZ increased the expression of microRNA‑204 (miR‑204), as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and the level of p53 as determined with western blotting, two well‑characterized tumor suppressor genes. When miR‑204 expression was knocked down by introduction of an miR‑204 inhibitor, the inhibitory effect of OBZ was markedly reduced; however, when it was overexpressed, the inhibitory efficiency of OBZ was markedly higher, indicating that upregulation of miR‑204 is key for the efficacy of OBZ. Additionally, OBZ was demonstrated with RT‑qPCR to repress the expression of the androgen receptor, and by western blotting to reduce prostate‑specific androgen in 22Rv1 cells. The results suggest that OBZ has potential for clinical use in the treatment of recurrent PCa.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
3	Peyromaure M, Valéri A, Rebillard X, Beuzeboc P, Richaud P, Soulié M and Salomon L: CCAFU: Characteristics of prostate cancer in men less than 50-year-old. Prog Urol. 19:803–809. 2009. View Article : Google Scholar : PubMed/NCBI
4	Crouzet S, Rouviere O, Martin X and Gelet A: High-intensity focused ultrasound as focal therapy of prostate cancer. Curr Opin Urol. 24:225–230. 2014. View Article : Google Scholar : PubMed/NCBI
5	Zhao X and Chua KJ: Regulating the cryo-freezing region of biological tissue with a controlled thermal device. Med Eng Phys. 36:325–334. 2014. View Article : Google Scholar : PubMed/NCBI
6	Smaletz O, Scher HI, Small EJ, Verbel DA, McMillan A, Regan K, Kelly WK and Kattan MW: Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J Clin Oncol. 20:3972–3982. 2002. View Article : Google Scholar : PubMed/NCBI
7	Asmane I, Céraline J, Duclos B, Rob L, Litique V, Barthélémy P, Bergerat JP, Dufour P and Kurtz JE: New strategies for medical management of castration-resistant prostate cancer. Oncology. 80:1–11. 2011. View Article : Google Scholar : PubMed/NCBI
8	Saad F and Hotte SJ: Guidelines for the management of castrate-resistant prostate cancer. Can Urol Assoc J. 4:380–384. 2010. View Article : Google Scholar : PubMed/NCBI
9	Petrylak DP: Current state of castration-resistant prostate cancer. Am J Manag Care. 19 18 Suppl:S358–S365. 2013.PubMed/NCBI
10	de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, et al: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 364:1995–2005. 2011. View Article : Google Scholar : PubMed/NCBI
11	Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, et al: Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 367:1187–1197. 2012. View Article : Google Scholar : PubMed/NCBI
12	Tanimoto T, Hori A and Kami M: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 363:1966; author reply 1967–8. 2010.
13	Joung JY, Ha YS and Kim IY: Radium Ra 223 dichloride in castration-resistant prostate cancer. Drugs Today (Barc). 49:483–490. 2013. View Article : Google Scholar
14	Pantziarka P, Bouche G, Meheus L, Sukhatme V and Sukhatme VP: Repurposing drugs in your medicine cabinet: Untapped opportunities for cancer therapy? Future Oncol. 11:181–184. 2015. View Article : Google Scholar
15	Pruksachatkunakorn C, Damrongsak M and Sinthupuan S: Sulfur for scabies outbreaks in orphanages. Pediatr Dermatol. 19:448–453. 2002. View Article : Google Scholar
16	Kenawi MZ, Morsy TA, Abdalla KF and el Hady HM: Treatment of human scabies by sulfur and permethrin. J Egypt Soc Parasitol. 23:691–696. 1993.
17	Duan F, Li Y, Chen L, Zhou X, Chen J, Chen H and Li R: Sulfur inhibits the growth of androgen-independent prostate cancer. Oncol Lett. 9:437–441. 2015. View Article : Google Scholar
18	Pantziarka P, Sukhatme V, Bouche G, Meheus L and Sukhatme VP: Repurposing drugs in oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience. 9:5212015. View Article : Google Scholar
19	Theodorides VJ, Chang J, DiCUOLLO CJ, Grass GM, Parish RC and Scott GC: Oxibendazole, a new broad spectrum anthelmintic effective against gastrointestinal nematodes of domestic animals. Br Vet J. 129:xcontdvii–scvi. 1973. View Article : Google Scholar
20	Kates KC, Colglazier ML and Enzie FD: Oxibendazole: Critical anthelmintic trials in equids. Vet Rec. 97:442–444. 1975.
21	Theodorides VJ, Nawalinski T, Freeman JF and Murphy JR: Efficacy of oxibendazole against gastrointestinal nematodes of cattle. Am J Vet Res. 37:1207–1209. 1976.
22	Overgaauw PA and Boersema JH: Anthelmintic efficacy of oxibendazole against some important nematodes in dogs and cats. Vet Q. 20:69–72. 1998. View Article : Google Scholar
23	Rao PS, Ray UK, Gupta PB, Rao DV, Islam A, Rajput P and Mukkanti K: Identification, isolation and characterization of new impurity in rabeprazole sodium. J Pharm Biomed Anal. 52:620–624. 2010. View Article : Google Scholar
24	Gaba M, Singh S and Mohan C: Benzimidazole: An emerging scaffold for analgesic and anti-inflammatory agents. Eur J Med Chem. 76:494–505. 2014. View Article : Google Scholar
25	He Y, Yang J, Wu B, Risen L and Swayze EE: Synthesis and biological evaluations of novel benzimidazoles as potential antibacterial agents. Bioorg Med Chem Lett. 14:1217–1220. 2004. View Article : Google Scholar
26	Li Y, Tan C, Gao C, Zhang C, Luan X, Chen X, Liu H, Chen Y and Jiang Y: Discovery of benzimidazole derivatives as novel multi-target EGFR VEGFR-2 and PDGFR kinase inhibitors. Bioorg Med Chem. 19:4529–4535. 2011. View Article : Google Scholar
27	Velik J, Baliharová V, Fink-Gremmels J, Bull S, Lamka J and Skálová L: Benzimidazole drugs and modulation of biotransformation enzymes. Res Vet Sci. 76:95–108. 2004. View Article : Google Scholar
28	Králová V, Hanušová V, Staňková P, Knoppová K, Čáňová K and Skálová L: Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines. Anticancer Drugs. 24:911–919. 2013. View Article : Google Scholar
29	Hanusova V, Skalova L, Kralova V and Matouskova P: Potential anti-cancer drugs commonly used for other indications. Curr Cancer Drug Targets. 15:35–52. 2015. View Article : Google Scholar
30	Sridhar SS, Freedland SJ, Gleave ME, Higano C, Mulders P, Parker C, Sartor O and Saad F: Castration-resistant prostate cancer: From new pathophysiology to new treatment. Eur Urol. 65:289–299. 2014. View Article : Google Scholar
31	Debes JD and Tindall DJ: Mechanisms of androgen-refractory prostate cancer. N Engl J Med. 351:1488–1490. 2004. View Article : Google Scholar
32	Nagabhushan M, Miller CM, Pretlow TP, Giaconia JM, Edgehouse NL, Schwartz S, Kung HJ, de Vere WR, Gumerlock PH, Resnick MI, et al: CWR22: The first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar. Cancer Res. 56:3042–2046. 1996.PubMed/NCBI
33	Shen MM and Abate-Shen C: Molecular genetics of prostate cancer: New prospects for old challenges. Genes Dev. 24:1967–2000. 2010. View Article : Google Scholar : PubMed/NCBI
34	Sramkoski RM, Pretlow TG II, Giaconia JM, Pretlow TP, Schwartz S, Sy MS, Marengo SR, Rhim JS, Zhang D and Jacobberger JW: A new human prostate carcinoma cell line, 22Rv1. In Vitro Cell Dev Biol Anim. 35:403–409. 1999. View Article : Google Scholar : PubMed/NCBI
35	Sturgeon CM, Hoffman BR, Chan DW, Ch'Ng SL, Hammond E, Hayes DF, Liotta LA, Petricoin EF, Schmitt M, Semmes OJ, et al: National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in clinical practice: Quality requirements. Clin Chem. 54:e1–e10. 2008. View Article : Google Scholar : PubMed/NCBI
36	Sardana G, Jung K, Stephan C and Diamandis EP: Proteomic analysis of conditioned media from the PC3, LNCaP, and 22Rv1 prostate cancer cell lines: Discovery and validation of candidate prostate cancer biomarkers. J Proteome Res. 7:3329–3338. 2008. View Article : Google Scholar : PubMed/NCBI
37	Li G, Petiwala SM, Nonn L and Johnson JJ: Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells. Biochem Biophys Res Commun. 453:75–80. 2014. View Article : Google Scholar : PubMed/NCBI
38	Kasimsetty SG, Bialonska D, Reddy MK, Thornton C, Willett KL and Ferreira D: Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells. J Agric Food Chem. 57:10636–10644. 2009. View Article : Google Scholar : PubMed/NCBI
39	Yang F, Jiang X, Song L, Wang H, Mei Z, Xu Z and Xing N: Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo. Oncol Rep. 35:1602–1610. 2016. View Article : Google Scholar : PubMed/NCBI
40	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
41	McDonald ER III, Wu GS, Waldman T and El-Deiry WS: Repair defect in p21 WAF1/CIP1-/-human cancer cells. Cancer Res. 56:2250–2255. 1996.PubMed/NCBI
42	Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM and Fornace AJ Jr: Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 266:1376–1380. 1994. View Article : Google Scholar : PubMed/NCBI
43	Theodorides VJ, DiCuollo CJ, Nawalinski T, Miller CR, Murphy JR, Freeman JF, Killeen JC Jr and Rapp WR: Toxicologic and teratologic studies of oxibendazole in ruminants and laboratory animals. Am J Vet Res. 38:809–814. 1977.PubMed/NCBI
44	Stenman UH: Prostate-specific antigen, clinical use and staging: An overview. Br J Urol. 79 Suppl 1:S53–S60. 1997. View Article : Google Scholar
45	Heinlein CA and Chang C: Androgen receptor in prostate cancer. Endocr Rev. 25:276–308. 2004. View Article : Google Scholar : PubMed/NCBI
46	Kim J and Coetzee GA: Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem. 93:233–241. 2004. View Article : Google Scholar : PubMed/NCBI
47	Ding M, Lin B, Li T, Liu Y, Li Y, Zhou X, Miao M, Gu J, Pan H, Yang F, et al: A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells. Oncotarget. 6:7686–7700. 2015. View Article : Google Scholar : PubMed/NCBI
48	Hermeking H: The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–199. 2010. View Article : Google Scholar : PubMed/NCBI
49	Östling P, Leivonen SK, Aakula A, Kohonen P, Mäkelä R, Hagman Z, Edsjö A, Kangaspeska S, Edgren H, Nicorici D, et al: Systematic analysis of microRNAs targeting the androgen receptor in prostate cancer cells. Cancer Res. 71:1956–1567. 2011. View Article : Google Scholar : PubMed/NCBI
50	Shi XB, Xue L, Ma AH, Tepper CG, Gandour-Edwards R, Kung HJ and DeVere WR: Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells. Oncogene. 32:4130–4138. 2013. View Article : Google Scholar : PubMed/NCBI
51	Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, Gallo CA, Plas DR, Biesiada J, Meller J and Czyzyk-Krzeska MF: VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 21:532–546. 2012. View Article : Google Scholar : PubMed/NCBI
52	Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, et al: miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 3:e4232012. View Article : Google Scholar : PubMed/NCBI
53	Ying Z, Li Y, Wu J, Zhu X, Yang Y, Tian H, Li W, Hu B, Cheng SY and Li M: Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype. Cancer Res. 73:990–999. 2013. View Article : Google Scholar : PubMed/NCBI
54	Tai S, Sun Y, Squires JM, Zhang H, Oh WK, Liang CZ and Huang J: PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate. 71:1668–1679. 2011. View Article : Google Scholar : PubMed/NCBI
55	Palapattu GS, Wu C, Silvers CR, Martin HB, Williams K, Salamone L, Bushnell T, Huang LS, Yang Q and Huang J: Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate. 69:787–798. 2009. View Article : Google Scholar : PubMed/NCBI
56	Simon RA, di Sant'Agnese PA, Huang LS, Xu H, Yao JL, Yang Q, Liang S, Liu J, Yu R, Cheng L, et al: CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers. Hum Pathol. 40:252–258. 2009. View Article : Google Scholar : PubMed/NCBI
57	Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 17:211–215. 2011. View Article : Google Scholar : PubMed/NCBI
58	Yin Y, Zhang B, Wang W, Fei B, Quan C, Zhang J, Song M, Bian Z, Wang Q, Ni S, et al: miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clin Cancer Res. 20:6187–6199. 2014. View Article : Google Scholar : PubMed/NCBI
59	Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, Lynch J, Bray IM, O'Meara A, Tracey L, et al: MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer. 107:967–976. 2012. View Article : Google Scholar : PubMed/NCBI
60	Liu J and Li Y: Trichostatin A and Tamoxifen inhibit breast cancer cell growth by miR-204 and ERα reducing AKT/mTOR pathway. Biochem Biophys Res Commun. 467:242–247. 2015. View Article : Google Scholar : PubMed/NCBI
61	van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL, Nordeen SK, Miller GJ and Lucia MS: Molecular characterization of human prostate carcinoma cell lines. Prostate. 57:205–225. 2003. View Article : Google Scholar : PubMed/NCBI
62	Wen S, Niu Y, Lee SO and Chang C: Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer Treat Rev. 40:31–40. 2014. View Article : Google Scholar : PubMed/NCBI
63	Vashchenko N and Abrahamsson PA: Neuroendocrine differentiation in prostate cancer: Implications for new treatment modalities. Eur Urol. 47:147–155. 2005. View Article : Google Scholar : PubMed/NCBI
64	Jin RJ, Wang Y, Masumori N, Ishii K, Tsukamoto T, Shappell SB, Hayward SW, Kasper S and Matusik RJ: NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. Cancer Res. 64:5489–5495. 2004. View Article : Google Scholar : PubMed/NCBI
65	Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, et al: Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 1:487–495. 2011. View Article : Google Scholar : PubMed/NCBI
66	Li W, Cohen A, Sun Y, Squires J, Braas D, Graeber TG, Du L, Li G, Li Z, Xu X, et al: The role of CD44 in glucose metabolism in prostatic small cell neuroendocrine carcinoma. Mol Cancer Res. 14:344–353. 2016. View Article : Google Scholar : PubMed/NCBI
67	Chi SW: Structural insights into the transcription-independent apoptotic pathway of p53. BMB Rep. 47:167–172. 2014. View Article : Google Scholar : PubMed/NCBI
68	Huang YX, Zhou JX, Xue ZQ, Wu YX, Chen JY, Wu HZ, Ji MH, Shen YP, Cao GQ, Wu ZX, et al: Clinical observations on the treatment of hookworm, Ascaris and Trichuris infection with oxibendazole. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 8:100–103. 1990.(In Chinese). PubMed/NCBI