Abstract
The chemotherapeutic agents Doxorubicin and Paclitaxel have been questioned for some time, due to the negative effects observed in some patients when used in high concentrations, which has limited their use. Based on this problem, this study aimed to determine the in vitro effect of Croton malambo extract on human cancer cell lines and its possible interaction with both drugs. The following drugs were studied: Doxorubicin and Paclitaxel, and the extract of C. malambo in the breast cancer cell lines MCF-7 and prostate cancer cell lines PC3. Sulforhodamine B was used to determine cytotoxicity. The nature of the interactions between the natural products and the chemotherapeutic drugs was analyzed by calculating the corresponding combination index (CI). It was found that the extract has no cytotoxic effect but a cytostatic effect on the studied cell lines. The Doxorubicin/C. malambo combinations allowed reducing the drug concentration from 3.9 to 4.8 times to inhibit cell viability by 50% in the PC3 line, while for MCF-7, a dose reduction index of 2.29 was obtained. Regarding the combination of the extract and Paclitaxel, it only showed a synergistic effect on the cell viability of the PC3 line. The findings show the pharmacological potential of the C. malambo extract and open the doors to new studies both in vitro and in vivo that can demonstrate the ability to achieve synergism and reduce the therapeutic concentrations of both drugs.
References
Organización Panamericana de la Salud (OPS). 2014. El Cáncer en la Región de las Américas, 2014. Enlace: OPS-Nota-Informativa-Cancer-2014.pdf. Disponible en: https://www.paho.org/es/temas/cancer.
Velásquez, C., González, M., Berrouet, M. & Jaramillo, N. (2016). Cardiotoxicidad inducida por la quimioterapia desde las bases moleculares hasta la perspectiva clínica. Rev Colomb Cardiol., 23(2), 104-111.
https://doi.org/10.1016/j.rccar.2015.10.002
Madonna, R. (2017). Diagnóstico y prevención de la cardiotoxicidad inducida por fármacos antineoplásicos: de la imagen a las tecnologías «ómicas». Rev Española Cardiol., 70(7), 576-582.
https://doi.org/10.1016/j.recesp.2016.12.032
Mattioli, R., Ilari, A., Colotti, B., Mosca, L., Fazi, F. & Colotti, G. (2023). Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming. Mol Asp Med., 93, 101205. https://doi.org/10.1016/j.mam.2023.101205.
https://doi.org/10.1016/j.mam.2023.101205
Mielke, S., Sparreboom, A., Steinberg, S., Gelderblom, H., Unger, C., Behringer, D. & Mross, K. (2005). Association of paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res., 11(13), 4843-4850. https://doi.org/10.1158/1078-0432.CCR-05-0298.
https://doi.org/10.1158/1078-0432.CCR-05-0298
Newman, D. & Cragg, G. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020 Mar 27;83(3):770-803. https://doi: 10.1021/acs.jnatprod.9b01285.
https://doi.org/10.1021/acs.jnatprod.9b01285
Suárez, A. & Chávez, K. (2018). Appraisal of Medicinal Plants with Anticancer Properties in South America. En M. S. Akhtar & M. K. Swamy (Eds.), Anticancer plants: Properties and Application: Volume 1 (pp. 229-283). Springer. https://doi.org/10.1007/978-981-10-8548-2_11
https://doi.org/10.1007/978-981-10-8548-2_11
Sharma, V., Kumar, D., Dev, K., & Sourirajan, A. (2023). Anticancer activity of essential oils: Cell cycle perspective. South African Journal of Botany, 157, 641-647. https://doi.org/10.1016/j.sajb.2023.04.031
https://doi.org/10.1016/j.sajb.2023.04.031
Thronicke, A., Schad, F., Debus, M., Grabowski, J., & Soldner, G. (2022). Viscum album L. Therapy in Oncology: An Update on Current Evidence. Complementary Medicine Research, 29(4), 362-368. https://doi.org/10.1159/000524184
https://doi.org/10.1159/000524184
Salatino, A., Faria-Salatino, M. & Negri, G. (2007). Traditional uses, Chemistry and Pharmacology of Croton species (Euphorbiaceae). J Braz Chem Soc. 18, 11-33. https://doi.org/10.1590/S0103-50532007000100002
https://doi.org/10.1590/S0103-50532007000100002
Godoy, G., Ojeda, L., León, V., Escalona, F., Mansilla, D., Brewer, M. & Noguera-Machado, N. (2020). Antimicrobial potential of Croton gossypiifolius (Euphorbiaceae) latex on species associated with human infections. Arnaldoa, 27(1), 247-255. http://dx.doi.org/10.22497/arnaldoa.271.27115
Suárez, A., Chavez, K., Mateu, E., Compagnone, R., Muñoz, A., Sojo, F., Arvelo, F., Mijares, M. & De Sanctis, J. (2009). Cytotoxic activity of seco-entkaurenes from Croton caracasana on human cancer cell lines. Nat Prod Commun. 4, 1547-1550.
https://doi.org/10.1177/1934578X0900401117
Suárez, A. (2023). An update on phytochemistry and pharmacology of Croton malambo H. Karst. Rev Facul Farma UCV., 86,1-2.
https://doi.org/10.54305/RFFUCV.2023.86.1-2.2
Suarez, A., Salazar, M., Compagnone, R., Tillet, S., Delle-Monache, F., & Digiulio, (2003). Antinociceptive and anti-inflammatory effects of Croton malambo aqueous extract, J Ethnopharmacol. 88 (1), 11-14. http://dx.doi.org/10.1016/S0378-8741(03)00179-X
https://doi.org/10.1016/S0378-8741(03)00179-X
Mateu, E., Chavez, K., Riina R., Compagnone, R., Delle-Monache, F. & Suárez A. (2012). New 3,4-seco-ent-kaurene dimmers from Croton micans. Nat Prod. Commun. 7, 5-8.
https://doi.org/10.1177/1934578X1200700104
Gupta, E., Kaushik, S., Purwar, S., Sharma, R., Balapure, A. & Sundaram S. (2017). Anticancer Potential of Steviol in MCF-7 Human Breast Cancer Cells. Pharmacogn Mag. 13(51):345-350. https://doi.org/10.4103/pm.pm_29_17.
https://doi.org/10.4103/pm.pm_29_17
Raeisi, F., Raeisi, E., Heidarian, E., Shahbazi-Gahroui, D. & Lemoigne, Y. (2019). Bromelain inhibitory effect on colony formation: an: in vitro: study on human AGS, PC3, and MCF-7 Cancer Cells. J Med Signals Sens, 9(4), 267-273. https://doi.org/10.4103/jmss.JMSS_42_18
https://doi.org/10.4103/jmss.JMSS_42_18
Vichai V. & Kirtikara K. (2006). Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc. 1, 1112-1116. https://doi.org/10.1038/nprot.2006.179
https://doi.org/10.1038/nprot.2006.179
Suárez, A., Vásquez, L., Taddei, A., Arvelo, F. & Compagnone, R. (2008). Antibacterial and cytotoxic activity of leaf essential oil of Croton malambo. J Essent Oil Bearing Plants. 11(2), 208-213. https://doi.org/10.1080/0972060X.2008.10643622
https://doi.org/10.1080/0972060X.2008.10643622
Caro-Fuentes, D., Ocampo-Buendía, Y., Ospina-Mateus, L., Salas-Díaz, R., Díaz-Castillo, F.& Franco-Ospina, L. (2019). Extractos del Caribe Colombiano con actividad antiproliferativa frente a líneas celulares de cáncer de pulmón. Rev Cub Farma. Disponible en: https://revfarmacia.sld.cu/index.php/far/article/view/283
Muñoz-Acevedo, A., Carlos, E., Rodríguez, J., Aristizábal-Córdoba, S. & Kouznetsov, V. (2014). Estudio químico-biológico de los aceites esenciales de Croton malambo H. Karst y su componente mayoritario, metileugenol. Bol Latinoam Caribe Plant Med Aroma., 13(4), 336-343.
Suárez, A., Vásquez, L., Manzano, M., & Compagnone, R. (2005). Essential oil composition of Croton cuneatus and Croton malambo growing in Venezuela. Flavour and Fragrance Journal, 20(6), 611-614. https://doi.org/10.1002/ffj.1498
https://doi.org/10.1002/ffj.1498
Morales, A., Pérez, P., Mendoza, R., Compagnone, R., Suarez, A., Arvelo, F., Ramirez, J. & Galindo-Castro, I. (2005). Cytotoxic and proapoptotic activity of ent-16beta-17alpha-dihydroxykaurane on human mammary carcinoma cell line MCF-7. Cancer Lett. 31;218(1):109-16. https://doi: 10.1016/j.canlet.2004.07.009.
https://doi.org/10.1016/j.canlet.2004.07.009
Vivas, J. (2010). Efecto Citotóxico de seco-ent-kauranos de Croton micans en células PC3 (cáncer de próstata) y HeLa (cáncer de útero): Combinación con compuestos seco-ent-kauranos y fármacos antitumorales. Tesis Doctoral. Universidad Central de Venezuela. Dispobible: http://hdl.handle.net/10872/8490
Taylor, P., Colman, L., & Bajoon, J. (2014). The search for plants with anticancer activity: Pitfalls at the early stages. J Ethnopharmacol. 158, 246-254. https://doi: 10.1016/j.jep.2014.10.034
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