Efecto del tratamiento con ácido fólico y carboplatino sobre la viabilidad de células no tumorales
DOI:
https://doi.org/10.24215/18536387e094Palabras clave:
micronutrientes, agentes quimioterapéuticos, viabilidad celularResumen
Las células cancerígenas están muy adaptadas y suelen ser resistentes a los agentes antitumorales, lo cual impedimenta una terapia efectiva contra el cáncer. Sin embargo, en estas células se encuentran factores que pueden modificar la respuesta al tratamiento quimioterapéutico. Resultados previos, obtenidos en células tumorales HeLa, demostraron que el ácido fólico (AF) combinado con el carboplatino (CBP) permitía bajar la dosis de CBP utilizada y aumentar la actividad del compuesto platinado. En este sentido, es imprescindible evaluar los efectos de dicho tratamiento en las células sanas. Por este motivo, se analizó el efecto del tratamiento combinado de AF y CBP in vitro sobre la viabilidad celular (ensayo MTT) utilizando sangre periférica de mujeres sanas. Los cultivos se realizaron por 48 horas a 37°C, durante las últimas 24 horas se efectuaron los tratamientos: 1. control negativo (CN); 2. control AF (900 nM); 3. control CBP (40,4 mM); 4. control de manitol (ML 40,4 mM); 5. combinado AF-CBP (900 nM-40,4 mM); 6. combinado AF-ML (900 nM-40,4 mM); 7. control positivo (CP etanol 10%). Los cultivos que recibieron la combinación AF-CBP presentaron una viabilidad similar a la observada para el CN. Por el contrario, en los cultivos que recibieron el tratamiento sólo con CBP la viabilidad disminuyó de manera estadísticamente significativa respecto de dicho control. Estos hallazgos podrían resultar un aporte explorando el uso del AF en protocolos basados en agentes platinados, con el fin de reducir las dosis en el tratamiento de pacientes y la aparición de efectos secundarios.
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Barata, F. (2008). Pemetrexed em segunda linha no carcinoma do pulmão de não pequenas células [Pemetrexed de segunda línea en el carcinoma pulmonar de células no pequeñas]. Revista Portuguesa de Pneumonología, 14(2), S21-26. https://doi.org/10.1016/S0873-2159(15)30311-1
Batra, V. y Devasagayam, T. P. A. (2009). Interaction between cytotoxic effects of γ-radiation and folate deficiency in relation to choline reserves. Toxicology, 255(1-2), 91-99. https://doi.org/10.1016/j.tox.2008.10.008
Ceresoli, G. L., Zucali, P. A., Favaretto, A. G., Grossi, F., Bidoli, P., Del Conte, G., Ceribelli, A., Bearz, A., Morenghi, E., Cavina, R., Marangolo, M., Soto Parra., H. J. y Santoro, A. (2006). Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. Journal of Clinical Oncology, 24(9), 1443-1448. https://doi.org/10.1200/JCO.2005.04.3190
Chaudhury, A., Das, S., Bunte, R. M. y Chiu, G. N. C. (2012). Potent therapeutic activity of folate receptortargeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft. International Journal of Nanomedicine, 7, 739-751. https://doi.org/10.2147/IJN.S26172
Choi, S.-W. y Mason, J. B. (2000). Folate and carcinogenesis: An integrated scheme. The Journal of Nutrition, 130(2), 129-132. https://doi.org/10.1093/jn/130.2.129
Cohen, S. M. y Lippard, S. J. (2001). Cisplatin: From DNA damage to cancer chemotherapy. Progress in Nucleic Acid Research and Molecular Biology, 67, 93-130. https://doi.org/10.1016/s0079-6603(01)67026-0
Concha-Cisternas, Y., Martínez-Sanguinetti, M. A., Leiva, A. M., Garrido-Méndez, A., Matus-Castillo, C., Díaz-Martínez, X., Salas, C., Ramírez-Alarcón, K., Martorell, M., Cigarroa, I., Lassare-Laso, N., Troncoso, C., de Moraes Ferrari, G. L., Labraña, A. M., Parra, S., Petermann-Rocha, F. y Celis-Morales, C. (2020). Nivel de actividad física y sedentarismo en personas con diagnóstico de cáncer en Chile. Revista Médica de Chile, 148(2), 168-177. http://dx.doi.org/10.4067/s0034-98872020000200168
Conklin, K. A. (2000). Dietary antioxidants during cancer chemotherapy: Impact on chemotherapeutic effectiveness and development of side effects. Nutrition and Cancer, 37(1), 1-18. https://doi.org/10.1207/S15327914NC3701_1
Fenech, M. F. (2010). Dietary reference values of individual micronutrients and nutriomes for genome damage prevention: current status and a road map to the future. The American Journal of Clinical Nutrition, 91(5), 1438S-1454S. https://doi.org/10.3945/ajcn.2010.28674D
Gambaro, R. C, Seoane, A. y Padula G. (2023). Vitamin E protective effects on genomic and cellular damage caused by pediatric preventive supplementation for anaemia: An experimental model. British Journal of Nutrition, 129(3), 468-477. https://doi.org/10.1017/S0007114522001556
Garin, A., Manikhas, A., Biakhov, M., Chezhin, M., Ivanchenko, T., Krejcy, K., Karaseva, V. y Tjulandin, S. (2008). A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Breast Cancer Research and Treatment, 110(2), 309-315. https://doi.org/10.1007/s10549-007-9722-5
Gröber, U., Holzhauer, P., Kisters, K., Holick, M. F. y Adamietz, I. A. (2016). Micronutrients in oncological intervention. Nutrients, 8(3), 163. https://doi.org/10.3390/nu8030163
Hansen, M. F., Greibe, E., Skovbjerg, S., Rohde, S., Kristensen, A. C. M., Jensen T. R., Stentford, C., Kjær, K. H., Kronborg, C. S. y Martensen, P. M. (2015). Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha. Cellular Signalling, 27(7), 1356-1368. https://doi.org/10.1016/j.cellsig.2015.03.020
Ho, G.-Y., Woodward, N. y Coward, J. I. G. (2016). Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies. Critical Reviews in Oncology/Hematology, 102, 37-46. https://doi.org/10.1016/j.critrevonc.2016.03.014
Ji, J., Zuo, P. y Wang, Y.-L. (2015). Enhanced antiproliferative effect of carboplatin in cervical cancer cells utilizing folate-grafted polymeric nanoparticles. Nanoscale Research Letters, 10, 453. https://doi.org/10.1186/s11671-015-1162-2
Keys, H. M., Bundy, B. N., Stehman, F. B., Muderspach, L. I., Chafe, W. E., Suggs, C. L., III., Walker, J. L. y Gersell, D. (1999). Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. The New England Journal of Medicine, 340(15), 1154-1161. https://doi.org/10.1056/nejm199904153401503
Kimura, M., Umegaki, K., Higuchi, M., Thomas, P. y Fenech, M. (2004). Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes. The Journal of Nutrition, 134(1), 48-56. https://doi.org/10.1093/jn/134.1.48
Ledermann, J. A., Canevari, S. y Thigpen, T. (2015). Targeting the folate receptor: Diagnostic and therapeutic approaches to personalize cancer treatments. Annals of Oncology, 26(10), 2034-2043. https://doi.org/10.1093/annonc/mdv250
Liu, Y., Pu, Y., Sun, L., Yao, H., Zhao, B., Zhang, R. y Zhang, Y. (2016). Folic acid functionalized γ-cyclodextrin C₆₀, a novel vehicle for tumor-targeted drug delivery. Journal of Biomedical Nanotechnology, 12(7), 1393-1403. https://doi.org/10.1166/jbn.2016.2275
Lokich, J. y Anderson, N. (1998). Carboplatin versus cisplatin in solid tumors: an analysis of the Literature. Annals of Oncology, 9(3), 13-21.
Luangwattananun, P., Chiraphapphaiboon, W., Thuwajit, C., Junking, M. y Yenchitsomanus, P.-T. (2022). Activation of cytotoxic T lymphocytes by self-differentiated myeloid-derived dendritic cells for killing breast cancer cells expressing folate receptor Alpha protein. Bioengineered, 13(6), 14188-14203. https://doi.org/10.1080/21655979.2022.2084262
Moore, K. N., Herzog, T. J., Lewin, S., Giuntoli, R. L., Armstrong, D. K., Rocconi, R. P., Spannuth, W. A. y Gold, A. M. (2007). A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecologic Oncology, 105(2), 299-303. https://doi.org/10.1016/j.ygyno.2006.12.031
Morris, M., Eifel, P. J., Lu, J., Grigsby, P. W., Levenback, C., Stevens, R. E., Rotwan, M., Gershenson, D. M. y Mutch, D. G. (1999). Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. The New England Journal of Medicine, 340(15), 1137-1143. https://doi.org/10.1056/nejm199904153401501
Muggia, F. M. (1989). Overview of carboplatin: replacing, complementing, and extending the therapeutic horizons of cisplatin. Seminars in Oncology, 16(2 Suppl. 5), 7-13.
Nikoloff, N., Ponzinibbio, M. V., Padula, G., De Luca, J. C., Golijow, C. D. y Seoane, A. (2016). Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line. Toxicology in Vitro, 37, 142-147. https://doi.org/10.1016/j.tiv.2016.09.019
Organización Mundial de la Salud. (10 de agosto de 2024). Cáncer. https://www.who.int/es/healthtopics/cancer#tab=tab_1
Organización Mundial de la Salud. (10 de agosto de 2024). Cáncer cervicouterino. https://www.who.int/es/health-topics/cervical-cancer#tab=tab_1
Pett, M. y Coleman, N. (2007). Integration of high-risk human papillomavirus: A key event in cervical carcinogenesis? The Journal of Pathology, 212(4), 356-367. https://doi.org/10.1002/path.2192
Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maiman, M. A., Clarke-Pearson, D. L. y Insalaco, S. (1999). Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. The New England Journal of Medicine, 340(15), 1144-1153. https://doi.org/10.1056/nejm199904153401502
Shen, D.-W., Pouliot, L. M., Hall, M. D. y Gottesman, M. M. (2012). Cisplatin resistance: A cellular selfdefense mechanism resulting from multiple epigenetic and genetic changes. Pharmacological Reviews, 64(3), 706-721. https://doi.org/10.1124/pr.111.005637
Simon, G. R., Manegold, C., Barker, S. S., Treat, J. A., Visseren-Grul, C. y Obasaju C. (2013). Pemetrexed use in the adjuvant setting for completely resectable non-small-cell lung cancer. Clinical Lung Cancer, 14(6), 601-608. https://doi.org/10.1016/j.cllc.2013.06.001
Singh, N., Baldi, M., Kaur, J., Muthu, V., Prasad, K. T., Behera, D., Bal, A., Gupta, N. y Kapoor R. (2019). Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first-line treatment of patients with nonsquamous non-small cell lung cancer using pemetrexed-based chemotherapy: The PEMVITASTART randomized trial. Cancer, 125(13), 2203-2212. https://doi.org/10.1002/cncr.32028
Stratgraphics (version 5.1). (1994). Stratgraphics User Manual. Manugistics Inc.
Ströhle, A., Zänker, K. y Hahn, A. (2010). Nutrition in oncology: The case of micronutrients (Review). Oncology Reports, 24(4), 815-828. https://doi.org/10.3892/or.2010.815
Szefler, B., Czeleń, P. y Krawczyk, P. (2021). The affinity of carboplatin to B-vitamins and nucleobases. International Journal of Molecular Sciences, 22(7), 3634. https://doi.org/10.3390/ijms22073634
Wang, J. (2020). Combination treatment of cervical cancer using folate-decorated, pH-sensitive, carboplatin and paclitaxel co-loaded lipid-polymer hybrid nanoparticles. Drug Design, Development and Therapy, 14, 823-832. https://doi.org/10.2147/DDDT.S235098
Whiteside, M. A., Heimburger, D. C. y Johanning, G. L. (2004). Micronutrients and cancer therapy. Nutrition Reviews, 62(4), 142-147. https://doi.org/10.1111/j.1753-4887.2004.tb00036.x
Whitney, C. W., Sause, W., Bundy, B. N., Malfetano, J. H., Hannigan, E. V., Fowler, W. C. Jr., Clarke-Pearson, D. L. y Liao, S.-Y. (1999). Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology Group and Southwest Oncology Group study. Journal of Clinical Oncology, 17(5), 1339-1348. https://doi.org/10.1200/jco.1999.17.5.1339
Wu, J., Lyons, G. H., Graham, R. D. y Fenech, M. F. (2009). The effect of selenium, as selenomethionine, on genome stability and cytotoxity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay. Mutagenesis, 24(3), 225-232. https://doi.org/10.1093/mutage/gen074
Xia, W. y Low, P. S. (2010). Folate-targeted therapies for cancer. Journal of Medicinal Chemistry, 53(19), 6811-6824. https://doi.org/10.1021/jm100509v
Young, O., Ngo, N., Lin, L., Stanbery, L., Creeden, J. F., Hamouda, D. y Nemunaitis, J. (2023). Folate receptor as a biomarker and therapeutic target in solid tumors. Current Problems in Cancer, 47(1), 100917. https://doi.org/10.1016/j.currproblcancer.2022.100917
Zhang, Q. I., Xiang, G., Zhang, Y., Yang, K., Fan, W. O., Lin, J., Zeng, F. y Wu, J. (2006). Increase of doxorubicin sensitivity for folate receptor positive cells when given as the prodrug N-(phenylacetyl) doxorubicin in combination with folate-conjugated PGA. Journal of Pharmaceutical Sciences, 95(10), 2266-2275. https://doi.org/10.1002/jps.20714
Zhang, G.-Z., Jiao, S.-C. y Meng, Z.-T. (2010). Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Journal of Experimental & Clinical Cancer Research, 29, 38. https://doi.org/10.1186/1756-9966-29-38
Zinner, R. G., Fossella, F. V., Gladish, G. W., Glisson, B. S., Blumenschein, G. R. Jr., Papadimitrakopoulou, V. A., Pisters, K. M. W., Kim, E. S., Oh, Y. W., Peeples, B. O., Zhishen, Y., Curiel, R. E., Obasaju, C. K., Hong, W. K. y Herbst, R. S. (2005). Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of advanced nonsmall cell lung cancer. Cancer, 104(11), 2449-2456. https://doi.org/10.1002/cncr.21480
Zur Hausen, H. (1996). Papillomavirus infections—a major cause of human cancers. Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, 1288(2), F55-F78. https://doi.org/10.1016/0304-419x(96)00020-0
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