Antitumoral properties of butanolic fraction from leaves extract of Chrysobalanus icaco L. in breast and lung cancer cell lines.
Keywords:
Chrysobalanus icaco, abajeru, cancer, MDA-MB-231, A549Abstract
Infusion of leaves from Chrysobalanus icaco L., known as Icaco or Abajeru, is widely consumed in Brazil due to its therapeutic effects, such as hyperglycemia regulation, anti-inflammatory, analgesic and against chronic diarrhea. The aqueous and hydroalcoholic extract from Icaco also present anti-cancer properties, including colon cancer and leukemia. However, the antitumoral activity of the butanolic fraction still unknown. This study aimed to investigate the antitumoral properties of butanolic fraction against breast and lung cancer cell lines. Breast and lung cancer cell lines were incubated with the butanolic fraction (0.5, 1 and 5 µg.mL-1) for 24h. WST-1 and Trypan blue exclusion assays evaluated cell viability. The reactive oxygen species generation was measured, and the cell death pathway was analyzed by flow cytometry. The phytochemical profile was determined by thin-layer chromatography (TLC) analysis. The butanolic fraction presents triterpenes, flavonoids, and phenolic compounds as its major constituents. Cell proliferation of MDA-MB-231 and A549 were decreased by butanolic fraction (0.5, 1.0, and 5.0 µg.mL-1) treatment. Butanolic fraction (5.0 µg.mL-1) increase intracellular reactive oxygen species levels in MDA-MB-231, 118%, and in A549, 20%, cell lines. The loss of viability and reactive oxygen species increase was accompanied by apoptosis induction. The cellular migration of both cell lines was decreased by 13% in MDA-MB-231 and by 58% in A549 with the butanolic fraction of C. icaco. These results suggest that the butanolic fraction from Chrysobalanus icaco has anti-cancer properties against MDA-MB-231 and A549 cancer cells.
References
Araújo-Filho, H.G., Dias, J.D.S., Quintans-Júnior, L.J., Santos, M.R.V., White, P.A.S., Barreto, R.S.S., Barreto, A.S., Estevam, C.S., Araujo, S.S., Almeida, J.R.G.S., Menezes, I.R.A., Coutinho, H.D.M., & Quintans, J.S.S. Phytochemical screening and analgesic profile of the lyophilized aqueous extract obtained from Chrysobalanus icaco leaves in experimental protocols. PharmaceuticaL Biology 2016. 54: 3055-3062. DOI: 10.1080/13880209.2016.1204618 2. Barbosa-Filho, J.M., Vasconcelos, T.H.C., Alencar, A.A., Batista, L.M., Oliveira, R.A.G., Guedes, D.N., Falcão, H.S., Moura, M.D., Diniz, M.F.F.M., & Modesto-Filho, J. Plants and their active constituents from South Central, and North America with hypoglycemic activity. Revista Brasileira de Farmacognosia 2005. 15: 392-413. 3. BRASIL. IBGE e Sociedade Brasileira de Diabetes. Censo 2012. 4. Castilho, R.O. & Kaplan, M.A.C. Phytochemical study and antimicrobial activity of Chrysobalanus icaco. Chemistry of Natural Compounds 2011. 47. doi: 10.1007/s00436-013-3670-2. 5. Dantas, F.J.S., Moraes, M.O., Leitão, A.A.C., Lage, C.A.S., Cabral Neto, J.B., Carvalho, J.J., Bezerra, R.J.A.C., Bernardo Filho, M., & Caldeira De Araujo, A. Genotoxic effects of stannous chloride (SnCl2) in K562 cell line. Food and Chemical Toxicology 2002a. 40: 1493-1498. 6. Dantas, F.J.S., Mattos, J.C.P.De., Moraes, M.O., Boasquevisque, S,E., Lage, C.A.S., Cabral Neto, J.B., Leitão, A.A.C., Bernardo Filho, M., Bezerra, R.J.A.C., & Caldeiradearaujo, A. DNA damage in peripheral blood nuclear cells assesssed by comet assay from individuals submitted to scintigraphic examinations. Cellular and Molecular Biology 2002b. 48 (7): 789-792. 7. De Paulo, S.A., Balassiano, I.T., Silva, N.H., Castilho, R.O., Kaplan, M.A.C., Cabral, M., & De Paulo, M.G.C.C. Chrysobalanus icaco L. extract for antiangiogenic potential observation. International Journal of Molecular Medicine 2000. 5: 667-669. 8. Fernandes, J., Castilho, R.O., Costa, M.R., Wagner-Souza, K., Coelho Kaplan, M.A.C., Gattas, C.R. Pentacyclic triterpenes from Chrysobalanaceae species: cytotoxicity on multidrug resistant and sensitive leukemia cell lines. Cancer Letters 2003. 190: 165-169. 9. Ferreira-Machado, S.C., Rodrigues, M.P., & Nunes, A.P.M. Genotoxic potentiality of aqueous extract prepared from Chrysobalanus icacoL. leaves. Toxicology Letters, Netherlands 2004. 151: 481-487. 10. Fronza, M., Heinzmann, B., Hamburger, M., Laufer, S. & Merfort I. Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts. Journal of Ethnopharmacology 2009. 126: 463–467. 11. Guimarães, L. P.T.P., Rocha, G. G., De Queiroz, R. M., Martins, C. A., Christina Maeda Takiya, C. M. & Gattass, C. R. Pomolic acid induces apoptosis and inhibits multidrug resistance protein MRP1 and migration in glioblastoma cells. Oncology reports 2017. 38: 2525-2534. doi: 10.3892/or.2017.5895. 12. Jiao, D. & Zhang, X.D. Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway.. Oncology Reports 2016. 36: 342-348. doi: 10.3892/or.2016.4777. 13. Kida, K., Ishikawa, T., Yamada, A., Shimizu, D., Tanabe, M., Sasaki, T., Ichikawa, Y., & Endo, I. A prospective feasibility study of sentinel node biopsy by modified Indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer. Eur J SurgOncol 2015. 41: 566-570. doi: 10.1016/j.ejso.2014.10.066. 14. Kim, B., Kim, J. & Park, B. Pomolic Acid Inhibits Invasion of Breast Cancer Cells Through the Suppression of CXC Chemokine Receptor Type 4 Expression. Journal of Cellular Biochemistry 2016. 117: 1296-1307. doi: 10.1002/jcb.25417 15. Nunes, A.P.M., Machado, S.C.F., Dantas, F.J.S., Mattos, J.C.P., Caldeira De Araujo, A. Analysis of genotoxic potentiality of stevioside by comet assay. Food and Chemical Toxicology 2007. 45: 662-666. 16. Schmidt, C., Fronza, M., Goettert, M., Geller, F., Luik, S., Flores, E.M.M., Bittencourt, C.F., Zanetti, G.D., Heinzmanne, B.M., Laufer, S. & Merfort I. Biological studies on Brazilian plants used in wound healing. Journal of Ethnopharmacology 2009. 122: 523–532. 17. Silva, J.P.B., Peres, A.R.M.N., Thiago Portal Paixão, T.P., Silva, A.S.B., Baetas, A.C., Barbosa, W.L.R., Monteiro, M.C., & Andrade, M.A. Antifungal Activity of Hydroalcoholic Extract of Chrysobalanus icaco Against Oral Clinical Isolates of Candida Species. Pharmacognosy Res. 2017. 9: 96-100. doi: 10.4103/0974-8490.199772. 18. Venancio, V.O., Marques, M.C., Almeida, M.R., Mariutti, L.R.B., Souza, V.C.O., Fernando Barbosa Jr, F., Bianchi, M.L.P., Machado, C.M.M., Mercadante, A.Z., & Antunes, L.M.G. Chrysobalanus icaco L. fruits inhibit NADPH oxidase complex and protect DNA against doxorubicin-induced damage in Wistar male rats. Journal of Toxicology and Environmental Health 2016. 79 (20): 885-93. doi: 10.1080/15287394.2016.1193454. 19. Venancio, V.P., Cipriano, P.A., Kim, H., Antunes, L.M.G., Stephen T. Talcotta, S.T., & Mertens-Talcott, S.U. Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells. Food Funct. 2017. 8 (1): 307-314. doi: 10.1039/c6fo01498d. 20. White, P.A.S., Cercato, L.M., Batista, V.S., Camargo, E.A., De Lucca Jr, W., Oliveira, A.S., Silva, F.T., Goes, T.C., Oliveira, E.R.A., Moraes, V.R.S., Nogueira, P.C.L., De Oliveira e Silva, A.M., Quintas-Junior, L.J., Lima, B.S., Araújo, A.A.S., & Santos, M.R.V. Aqueous extract of Chrysobalanus icaco leaves, in lower doses, prevent fat gain in obese high-fat fed mice. Journal of Ethnopharmacology 2016. 179: 92-100. doi: 10.1016/j.jep.2015.12.047.
