Efectos del Mebendazol Sobre el Mecanismo de Apoptosis Mediado por Caspasa en Cultivos de Células Cancerosas

  • Mahmut Şahin Sivas Cumhuriyet University, Faculty of Veterinary, Department of Pharmacology and Toxicology. Sivas, Türkiye
  • Haki Kara Sivas Cumhuriyet University, Faculty of Veterinary, Department of Pharmacology and Toxicology. Sivas, Türkiye
Palabras clave: Apoptosis, anticáncer, mebendazol, paclitaxel, vincristina

Resumen

Este estudio se realizó para comparar el mebendazol en términos de sus efectos inductores de apoptosis e inhibidores de tubulina cuando se combina con vincristina y paclitaxel, ambos utilizados en el tratamiento del cáncer. En el estudio se utilizaron líneas celulares de fibroblastos de pulmón (MRC–5) y de carcinoma de pulmón de células pequeñas (NCI–H209). Se aplicaron concentraciones de mebendazol, vincristina y paclitaxel a 0,5 µM, 1 µM, 1,5 µM y 2 µM por separado a estas líneas celulares, así como en combinaciones. Después de que las células se mantuvieron en el medio de cultivo durante 24 horas después de la administración del fármaco, se realizaron experimentos de proliferación celular, niveles de ADN apoptótico, niveles de caspasa 3, 8 y 9 y experimentos de curación de heridas in vitro. Se determinó que el mebendazol suprimía la proliferación celular y la curación celular, aumentaba los niveles de caspasa–3, caspasa–8, caspasa–9 y la formación de ADN apoptótico en células cancerosas de pulmón NCI–H209. En comparación con los grupos que recibieron mebendazol y vincristina solos, se observó que la proliferación celular estaba más suprimida y que el nivel de apoptosis aumentó en las células cancerosas en los grupos que recibieron la combinación de los dos fármacos. Según los hallazgos obtenidos en el presente estudio, debemos creer que el mebendazol puede poseer actividad terapéutica contra las células cancerosas del pulmón (NCI–H209) debido a sus efectos inductores de apoptosis y supresores de la proliferación celular.

Descargas

La descarga de datos todavía no está disponible.

Citas

Doudican NA, Byron SA, Pollock PM, Orlow SJ. XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts. Anti–Cancer Drug. [Internet]. 2013; 24(2):181–188. doi: https://doi.org/f4hm8n

Nygren P, Fryknas M, Agerup B, Larsson R. Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. J. Cancer Res. Clin. Oncol. [Internet]. 2013; 139:2133–2140. doi: https://doi.org/f23r3k

Tapas M, Ji–ichiro S, Ramesh R, Roth JA. Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both in Vitro and in Vivo. Clin. Cancer Res. [Internet] 2002 [cited 27 Oct 2023]; 8(9):2963–2969. Available in: https://goo.su/qG52Bi

Sasaki J–i, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T. The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non–Small Cell Lung Cancer Cells. Mol. Cancer Ther. [Internet] 2002 [cited 27 Oct 2023]; 1(13):1201–1209. Available in: https://goo.su/rg8MD

Sawanyawisuth K, Williamson T, Wongkham S, Riggins R. Effect of the antiparasitic drug mebendazole on cholangiocarcinoma growth. Southeast Asian J. Trop. Med. Public Health. [Internet]. 2014 [cited 19 Oct 2023]; 45(6):1264. Available in: https://goo.su/YQusKKo

Chu S, Badar S, Morris DL, Pourgholami MH. Potent Inhibition of Tubulin Polymerisation and Proliferation of Paclitaxel–resistant 1A9PTX22 Human Ovarian Cancer Cells by Albendazole. Anti–cancer Res. [Internet]. 2009 [cited 19 Oct 2023]; 29(10):3791–3796. Available in: https://goo.su/Zuoue

Silverman JA, Deitcher SR. Marqibo® (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother. Pharmacol. [Internet]. 2013; 71(3):555–564. doi: https://doi.org/f4q3rg

Jordan M A, Wilson L. Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curr. Opin. Cell Biol. [Internet]. 1998; 10(1):123–130. doi https://doi.org/ddqjbz

Laclette J, Guerra G, Zetina C. Inhibition of tubulin polymerization by mebendazole. Biochem. Biophy. Res. Commun. [Internet]. 1980; 92(2):417–423. doi: https://doi.org/b55p2p

Katiyar S, Gordon V, McLaughlin G, Edlind TJA. Antiprotozoal activities of benzimidazoles and correlations with beta–tubulin sequence. Antimicrob. Agents Chemother. [Internet]. 1994; 38(9):2086–2090. doi: https://doi.org/mnqx

Morgan U, Reynoldson J, Thompson RJA. Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro. Antimicrob. Agents. [Internet]. 1993; 37(2):328–331. doi: https://doi.org/mnpg

Keese CR, Wegener J, Walker SR, Giaever I. Electrical wound–healing assay for cells in vitro. Proceedings of the National Academy of Sciences. [Internet]. 2004; 101(6):1554–1559. doi: https://doi.org/c8mh9w

Rodriguez LG, Wu X, Guan J–L. Wound–healing assay. In: Guan J–L, editor. Cell Migration. Methods Mol. Biol. Vol. 294. [Internet]. Totowa, NJ: Humana Press; 2005. p. 23–29. doi: https://doi.org/d4rcbq

Doudican N, Rodriguez A, Osman I, Orlow SJ. Mebendazole induces apoptosis via Bcl–2 inactivation in chemoresistant melanoma cells. Mol. Cancer Res. [Internet]. 2008; 6(8):1308–1315. doi: https://doi.org/dznd4t

Guerini AE, Triggiani L, Maddalo M, Bonù ML, Frassine F, Baiguini A, Alghisi A, Tomasini D, Borghetti P, Pasinetti N, Bresciani N, Magrini SM, Buglione M. Mebendazole as a candidate for drug repurposing in oncology: an extensive review of current literature. Cancers (Basel). [Internet]. 2019; 11(9):1284. doi: https://doi.org/gj2xmr

Martarelli D, Pompei P, Baldi C, Mazzoni G. Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice. Cancer Chemother. Pharmacol. [Internet]. 2008; 61(5):809–817. doi: https://doi.org/dq6mzb

Pinto LC, Mesquita FP, Soares BM, da Silva EL, Puty B, Oliveria EH, Burbano RR, Montenegro RC. Mebendazole induces apoptosis via C–MYC inactivation in malignant ascites cell line (AGP01). Toxicol. in Vitro. [Internet]. 2019; 60:305–312. doi: https://doi.org/mnqm

Wang X, Lou K, Song X, Ma H, Zhou X, Xu H, Wang W. Mebendazole is a potent inhibitor to chemoresistant T cell acute lymphoblastic leukemia cells. Toxicol. Appl. Pharmacol. [Internet]. 2020; 396:115001. doi: https://doi.org/mnqn

Lai SR, Castello S, Robinson A, Koehler J. In vitro anti‐tubulin effects of mebendazole and fenbendazole on canine glioma cells. Vet. Comp. Oncol. [Internet]. 2017; 15(4):1445–1454. doi: https://doi.org/mnqp

Figueroa–Masot XA, Hetman M, Higgins MJ, Kokot N, Xia Z. Taxol induces apoptosis in cortical neurons by a mechanism independent of Bcl–2 phosphorylation. J. NeuroSci. [Internet]. 2001; 21(13):4657–4667. doi: https://doi.org/mnqt

Dennison JB, Kulanthaivel P, Barbuch RJ, Renbarger JL, Ehlhardt WJ, Hall S. Selective metabolism of vincristine in vitro by CYP3A5. Drug Metab. Dispos. [Internet]. 2006; 34(8):1317–1327. doi: https://doi.org/cfg8z8

Hayot C, Farinelle S, De Decker R, Decaestecker C, Darro F, Kiss R, Damme MV. In vitro pharmacological characterizations of the anti–angiogenic and anti–tumor cell migration properties mediated by microtubule–affecting drugs, with special emphasis on the organization of the actin cytoskeleton. Int. J. Oncol. [Internet]. 2002; 21(2):417–425. doi: https://doi.org/mnqv

Mandel EM, Lewinskimd U, Djaldetti M. Vincristine‐induced myocardial infarction. Cancer. [Internet]. 1975; 36(6):1979–1982. doi: https://doi.org/bhms9c

Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. [Internet]. 2007; 35(4):495–516. doi: https://doi.org/b5hgfz

Turgut NH, Armagan G, Kasapligil G, Erdogan MA. Anti–cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells. Bratis. Lek. Listy. [Internet]. 2022; 123(11):813–821. doi: https://doi.org/mnqw

Zhang JH, Xu M. DNA fragmentation in apoptosis. Cell Res. 2000; 10:205–211. doi: https://doi.org/d3dnc3

Wang W, Zhu M, Xu Z, Li W, Dong X, Chen Y, Lin B, Li M. Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase–3 activity. Biol. Res. [Internet]. 2019; 52(36):1–10. doi: https://doi.org/gkx6tw

Wu Y, Zhao D, Zhuang J, Zhang F, Xu C. Caspase–8 and caspase–9 functioned differently at different stages of the cyclic stretch–induced apoptosis in human periodontal ligament cells. PLoS One. [Internet]. 2016; 11(12):e0168268. doi: https://doi.org/f9gx55

Yarrow JC, Perlman ZE, Westwood NJ, Mitchison TJ. A high–throughput cell migration assay using scratch wound healing, a comparison of image–based readout methods. BMC Biotechnol. [Internet]. 2004; 4:21. https://doi.org/c4nxzh

Maini PK, McElwain S, Leavesley D. Travelling waves in a wound healing assay. Appl. Math. Lett. [Internet]. 2004; 17(5):575–580. doi: https://doi.org/dst6pw

Publicado
2024-03-30
Cómo citar
1.
Şahin M, Kara H. Efectos del Mebendazol Sobre el Mecanismo de Apoptosis Mediado por Caspasa en Cultivos de Células Cancerosas. Rev. Cient. FCV-LUZ [Internet]. 30 de marzo de 2024 [citado 19 de abril de 2024];34(1):7. Disponible en: https://produccioncientificaluz.org/index.php/cientifica/article/view/41857
Sección
Medicina Veterinaria