Salinomicina comercial tiene actividad antiproliferativa sobre tres líneas celulares de cáncer en hipoxia natural a 3 600 msnm
Salinomicina comercial efectiva contra cáncer
DOI:
https://doi.org/10.47993/gmb.v48i2.1038Palabras clave:
agentes antineoplásicos, neoplasias del cuello uterino, neoplasias de la mama, neoplasias pulmonares, salinomicinaResumen
Resumen
La salinomicina es un compuesto prometedor como medicamento contra el cáncer debido a su acción antiproliferativa contra células madre de cáncer y su acción selectiva, es decir que no ataca células normales. Se ha mostrado resultados prometedores sobre la versión ultrapura del compuesto, pero aún no se ha evaluado la versión comercial, que actualmente es utilizada como suplemento alimenticio por veterinarios. Objetivo: Determinar la actividad antiproliferativa de la versión ultrapura y comercial de salinomicina sobre tres líneas celulares de cáncer. Métodos: Se realizo un estudio experimental in vitro transversal donde se evaluó el efecto antiproliferativo de dos versiones de salinomicina sobre las líneas Hela (células de cáncer cervicouterino), A549 (células de cáncer de pulmón) y MCF-7 (células de cáncer de mama) mediante el ensayo de citotoxicidad MTT y la evaluación de morfología celular apoptótica a las 48h y 72h de tratamiento. Además se evaluó las cantidades de salinomicina asimiladas por las líneas celulares a una altitud de 3 600 msnm. Resultados: Salinomicina en su versión comercial tiene una buena actividad antiproliferativa contra las líneas celulares HeLa, A549 y MCF-7. Ésta actividad es similar a la actividad del compuesto ultrapuro y al reportado por articulos previamente publicados. La asimilación de la salinomicina por las líneas celulares fue bastante baja, observandose que dentro de 72 horas de incubación todavia se observaba el 75% del compuesto en las concentraciones más altas. Los resultados sugieren que la versión comercial de salinomicina tiene el potencial de convertirse en una droga de bajo costo.
Métricas
Citas
Chakravarty D, Solit DB. Clinical cancer genomic profiling. Nat Rev Genet. 2021;22(8):483-501. Available from: https://doi.org/10.1038/s41576-021-00338-8 DOI: https://doi.org/10.1038/s41576-021-00338-8
Carbone M, Arron ST, Beutler B, Bononi A, Cavenee W, Cleaver JE, et al. Tumour predisposition and cancer syndromes as models to study gene–environment interactions. Nat Rev Cancer. 2020;20(9):533-49. Available from: https://doi.org/10.1038/s41568-020-0265-y DOI: https://doi.org/10.1038/s41568-020-0265-y
World Health Organization. Cancer in the Americas. Geneva: WHO; 2020. Available from: https://www.who.int/es/news-room/fact-sheets/detail/cancer
International Agency for Research on Cancer. Bolivia fact sheet. Lyon: IARC; 2022. Available from: https://gco.iarc.fr/today/en/fact-sheets-populations#countries
Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645-59. Available from: https://doi.org/10.1016/j.cell.2009.06.034 DOI: https://doi.org/10.1016/j.cell.2009.06.034
Lu D, Choi MY, Yu J, Castro JE, Kipps TJ, Carson DA. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A. 2011;108(32):13253-7. Available from: https://doi.org/10.1073/pnas.1110431108 DOI: https://doi.org/10.1073/pnas.1110431108
Tang QL, Zhao ZQ, Li JC, Liang Y, Yin JQ, Zou CY, et al. Salinomycin inhibits osteosarcoma by targeting its tumor stem cells. Cancer Lett. 2011;311(1):113-21. Available from: https://doi.org/10.1016/j.canlet.2011.07.016 DOI: https://doi.org/10.1016/j.canlet.2011.07.016
Lieke T, Ramackers W, Bergmann S, Klempnauer J, Winkler M, Klose J. Impact of salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro. BMC Cancer. 2012;12:466. Available from: https://doi.org/10.1186/1471-2407-12-466 DOI: https://doi.org/10.1186/1471-2407-12-466
Zhi QM, Chen XH, Ji J, Zhang JN, Li JF, Cai Q, et al. Salinomycin can effectively kill ALDH high stem-like cells on gastric cancer. Biomed Pharmacother. 2011;65(7):509-15. Available from: https://doi.org/10.1016/j.biopha.2011.06.006 DOI: https://doi.org/10.1016/j.biopha.2011.06.006
Verdoodt B, Vogt M, Schmitz I, Liffers ST, Tannapfel A, Mirmohammadsadegh A. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012;7(9):e44132. Available from: https://doi.org/10.1371/journal.pone.0044132 DOI: https://doi.org/10.1371/journal.pone.0044132
Boehmerle W, Muenzfeld H, Springer A, Huehnchen P, Endres M. Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. J Mol Med (Berl). 2014;92(8):889-900. Available from: https://doi.org/10.1007/s00109-014-1155-0 DOI: https://doi.org/10.1007/s00109-014-1155-0
Yue W, Hamaï A, Tonelli G, Bauvy C, Nicolas V, Tharinger H, et al. Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance. Autophagy. 2013;9(5):714-29. Available from: https://doi.org/10.4161/auto.23997 DOI: https://doi.org/10.4161/auto.23997
Antoszczak M. A medicinal chemistry perspective on salinomycin as a potent anticancer and anti-CSCs agent. Eur J Med Chem. 2019;164:366-77. Available from: https://doi.org/10.1016/j.ejmech.2018.12.057 DOI: https://doi.org/10.1016/j.ejmech.2018.12.057
Mai TT, Hamaï A, Hienzsch A, Cañeque T, Müller S, Wicinski J, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017;9(10):1025-33. Available from: https://doi.org/10.1038/nchem.2778 DOI: https://doi.org/10.1038/nchem.2778
Antoszczak M. A comprehensive review of salinomycin derivatives as potent anticancer and anti-CSCs agents. Eur J Med Chem. 2019;166:48-64. Available from: https://doi.org/10.1016/j.ejmech.2019.01.034 DOI: https://doi.org/10.1016/j.ejmech.2019.01.034
Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 2009;390(3):743-9. Available from: https://doi.org/10.1016/j.bbrc.2009.10.042 DOI: https://doi.org/10.1016/j.bbrc.2009.10.042
Riccioni R, Dupuis ML, Bernabei M, Petrucci E, Pasquini L, Mariani G, et al. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010;45(1):86-92. Available from: https://doi.org/10.1016/j.bcmd.2010.03.008 DOI: https://doi.org/10.1016/j.bcmd.2010.03.008
Zhou S, Wang F, Wong ET, Fonkem E, Hsieh TC, Wu JM, et al. Salinomycin: a novel anti-cancer agent with known anti-coccidial activities. Curr Med Chem. 2013;20(33):4095-101. Available from: https://doi.org/10.2174/15672050113109990199 DOI: https://doi.org/10.2174/15672050113109990199
Wang H, Zhang H, Zhu Y, Wu Z, Cui C, Cai F. Anticancer mechanisms of salinomycin in breast cancer and its clinical applications. Front Oncol. 2021;11:654428. Available from: https://doi.org/10.3389/fonc.2021.654428 DOI: https://doi.org/10.3389/fonc.2021.654428
Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986;89(2):271-7. Available from: https://doi.org/10.1016/0022-1759(86)90368-6 DOI: https://doi.org/10.1016/0022-1759(86)90368-6
Blanchflower WJ, Rice DA, Hamilton JT. Simultaneous high-performance liquid chromatographic determination of monensin, narasin and salinomycin in feeds using post-column derivatisation. Analyst. 1985;110(11):1283-7. Available from: https://doi.org/10.1039/an9851001283 DOI: https://doi.org/10.1039/an9851001283
Wickham H. ggplot2: Elegant graphics for data analysis. New York: Springer-Verlag; 2009. Available from: https://ggplot2-book.org/ DOI: https://doi.org/10.1007/978-0-387-98141-3
Rodrigo G, Almanza GR, Cheng Y, Peng J, Hamann M, Duan RD, et al. Antiproliferative effects of curcuphenol, a sesquiterpene phenol. Fitoterapia. 2010;81(7):762-6. Available from: https://doi.org/10.1016/j.fitote.2010.04.001 DOI: https://doi.org/10.1016/j.fitote.2010.04.001
Iturri JP, Rodrigo GD. Damsin, coronopilin and santamarin, esquiterpenelactones that manifest a cytotoxic activity, DNA damage capability and apoptosis capability on cancer cells lines A549, HeLa and Panc-1. Rev Boliv Quim. 2018;35(1):6-14. Available from: http://www.scielo.org.bo/scielo.php?script=sci_arttext&pid=S0250-54602018000100002&lng=es&nrm=iso
Tung CL, Chen JC, Wu CH, Peng YS, Chen WC, Zheng HY, et al. Salinomycin acts through reducing AKT-dependent thymidylate synthase expression to enhance erlotinib-induced cytotoxicity in human lung cancer cells. Exp Cell Res. 2017;357(1):59-66. Available from: https://doi.org/10.1016/j.yexcr.2017.04.026 DOI: https://doi.org/10.1016/j.yexcr.2017.04.026
Tefas LR, Barbălată C, Tefas C, Tomuță I. Salinomycin-based drug delivery systems: overcoming the hurdles in cancer therapy. Pharmaceutics. 2021;13(8):1120. Available from: https://doi.org/10.3390/pharmaceutics13081120 DOI: https://doi.org/10.3390/pharmaceutics13081120
Zhang S, Hu X, Sun M, Chen X, Le S, Wang X, et al. Potential role of hypobaric hypoxia environment in treating pan-cancer. Sci Rep. 2025;15(1):12942. Available from: https://doi.org/10.1038/s41598-024-84561-3 DOI: https://doi.org/10.1038/s41598-024-84561-3
Kamlund S, Strand D, Janicke B, Alm K, Oredsson S. Influence of salinomycin treatment on division and movement of individual cancer cells cultured in normoxia or hypoxia evaluated with time-lapse digital holographic microscopy. Cell Cycle. 2017;16(21):2128-38. Available from: https://doi.org/10.1080/15384101.2017.1380131 DOI: https://doi.org/10.1080/15384101.2017.1380131
Kim KY, Park KI, Kim SH, Yu SN, Lee D, Kim YW, et al. Salinomycin induces reactive oxygen species and apoptosis in aggressive breast cancer cells as mediated with regulation of autophagy. Anticancer Res. 2017;37(4):1747-58. Available from: https://ar.iiarjournals.org/content/anticanres/37/4/1747.full.pdf DOI: https://doi.org/10.21873/anticanres.11507
Awad L. Synthesis of chemical tools to improve water solubility and promote the delivery of salinomycin to cancer cells. Exp Ther Med. 2020;19(3):1835-43. Available from: https://doi.org/10.3892/etm.2019.8368 DOI: https://doi.org/10.3892/etm.2019.8368
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2025 Gaceta Médica Boliviana
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial 4.0.
