Estudos In silico sobre as atividades anticancerígenas do Eugenol presente no Cravo Da Índia (Syzygium aromaticum)

Autores

DOI:

https://doi.org/10.33448/rsd-v10i4.14165

Palavras-chave:

Eugenol; Anticancerígeno; Antimutagênico; In silico.

Resumo

Objetivo: Investigar as propriedades anticancerígenas do eugenol usando métodos In silico. Metodologia: é um artigo original utilizando a metodologia In silico atraves dos softwares PASS (Prediction of activity spectra for substances) online e GUSAR disponíveis de forma gratuita e livre. Resultados: Os resultados do sistema operacional online PASS demonstraram diversas atividades biológicas positiva, tais quais efeito antimutagênico, estimulante de caspase, tratamento pré neoplásico e agonista de apoptose tendo uma probabilidade de atividade (PA) bem superior a 0,700. Tais achados reforçam aos descritos na literatura que evidenciam um potencial antineoplásico devido o componente ter efeitos antioxidante, e estar vinculado a expressão de genes envolvidos na apoptose e inflamação. Tal como efeitos na regulação negativa de Bcl-2, COX-2 e IL-1ß, e ações na regulação positiva de P53, Bax e expressão ativa de Caspase-3, caspase-9 além de induzir a via da apoptose mitocondrial. Já pelo software GUSAR, foi observado a toxicidade, demonstrando que na categoria 4, estão as vias de administração intravenosa, oral, e subcutânea, indicando que é pouco tóxico. Já na categoria 5 enquadra-se a via intraperitoneal é relativamente atóxico. Tal achado ainda é obscuro e possui poucos artigos científicos para o embasamento. Conclusão: O Eugenol possui efeitos favoráveis para o tratamento e prevenção de diversos canceres e células mutagênicas, porém ainda há pouco conhecimento sobre a toxicidade deste componente. Assim, necessita de um maior aprofundamento sobre a temática.

Referências

Affonso, R. S., Rennó, M. N., Slana, G. B. C. A., & Franca, T. C. C.(2012). Chemical and Biological Aspects of the Essential Oil of Indian Cloves. Revista Virtual de Química, 4(2), 146-161, 2012. http://dx.doi.org/10.5935/1984-6835.20120012.

Ali, S., Prasad, R. Mahmood, A., Routray, I., Shinkafi, T.S., Sahin, K., & Kucuk, O. (2014). Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation. Journal Of Cancer Prevention, 19 (4), 288-300. http://dx.doi.org/10.15430/jcp.2014.19.4.288.

Ali, S., Prasad, R., Mahmood, A., Routray, I., Shinkafi, T. S., Sahin, K., & Kucuk, O. (2014). Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation. Journal Of Cancer Prevention, 19 (4), 288-300. http://dx.doi.org/10.15430/jcp.2014.19.4.288

Al-Sharif, I, Remmal, A, & Aboussekhra, A. (2013). Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation. BioMed Central Cancer, 13:600. https://dx.doi.org/10.1186/1471-2407-13-600.

Bezerra, D., Militão, G., Morais, M. D., & Sousa, D. D. (2017). The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment. Nutrients, 9(12), 1367-1382. http://dx.doi.org/10.3390/nu9121367.

Castaneda, C., A., Cortes, H. F., Gomez, H. L., & Ciruelos, E. M. (2010). The phosphatidyl inositol 3- kinase/AKT signaling pathway in breast cancer. Cancer Metastasis, v. 29, 751-759. https://doi.org/10.1007/s10555-010-9261-0.

Chiu, S. M, Xue L.Y., Usuda, J, Azizuddin K., & Oleinick, N. L. (2003). Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy. British Journal Of Cancer, 1590-1597. 10.1038/sj.bjc.6601298.

Danchin A., Medigue C., Gascuel O., Soldano H., & Henaut A. (1991). From data banks to data bases. Research in Microbiology, 142 (7-8), 913-6. Http://dx.doi.org/10.1016/0923-2508(91)90073-J

Derossi, D. R., Ito, K., Couto, F., José D. O., & Bacchi, C. E. (2003). Avaliação da expressão da proteína bcl-2 no carcinoma de mama: estudo em punção aspirativa por agulha fina, correlação com grau histológico em espécimes cirúrgicos correspondentes. Jornal Brasileiro de Patologia e Medicina Laboratorial, 39(3), 229-235. Http://dx.doi.org/10.1590/s1676-24442003000300010

Facchini, L. M., & Penn, L. Z. (1998). The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB Journal, 12(1), 633-51.

Faria, M. H. G, Patrocínio, R. M. S. V. Filho, M. O. M., & Rabenhorst, S. H. (2006). Expressão das proteínas BCL-2 e BAX em tumores astrocíticos humanos. Jornal Brasileiro de Patologia e Medicina Laboratorial, 42(4), 271-278. https://doi.org/10.1590/S1676-24442006000400008.

Fathy, M., Fawzy, M. A., Hintzsche, H., Nikaido, T., Dandekar, T., & Othman, E. M. (2019) Eugenol Exerts Apoptotic Effect and Modulates the Sensitivity of HeLa Cells to Cisplatin and Radiation. Molecule, 24(21), 3979-3393. http://dx.doi.org/10.3390/molecules24213979.

Fett, C., Agnes C., & Salles, A. B. C. F. (2002). A importância do gene p53 na carcinogênese humana. Revista Brasileira Hematologia Hemoterapia, 24(2), 85-89. http://dx.doi.org/10.1590/S1516-84842002000200004.

Filimonov, D. A, Lagunin, A.A, Gloriozova T. A., Rudik A. V., Druzhilovskii D. S., Pogodin, P. V., & Poroikov V. V. (2014). Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chemistry of Heterocyclic Compounds. 50 (3), 444–457.https://doi.org/10.1007/s10593-014-1496-1

Freitas, C. S. (2008). Estendendo o Conhecimento sobre a Família Her-Receptores para o Fator de Crescimento Epidérmico e seus ligantes às Malignidades Hematológicas. Revista Brasileira de Cancerologia, 1(54), 79-86. www1.inca.gov.br/rbc/n_54/v01/pdf/revisao_5_pag_79a86.pdf.

Fruman, D. A., & Rommel, C. (2014). PI3K and cancer: lessons, challenges and opportunities. Nature Reviews Drug Discovery, 13(2), 140-156. Http://dx.doi.org/10.1038/nrd4204.

Gatti, A. L., Witter, C., Gil, C. A., & Vitorino, S. D. S. (2015). Psychologically focused group intervention with the elderly: A qualitative research.Psicologia: Ciência e Profissão, 35(1), 20-39.

Ghayad, S., & Cohen, P. (2010). Inhibitors Of The PI3K/Akt/Mtor Pathway: new hope for breast cancer patients. Recent Patents On Anti-Cancer Drug Discovery. Bentham Science Publishers Ltd, 5(1), 29-57. http://dx.doi.org/10.2174/157489210789702208.

Gökalp, F. (2006). A Study On The Chemical Properties Of Eugenol And Eugenol Acetate, Clove Essential Oils. Sigma Journal Engineering And Natural Sciences Sigma, 3(34), 407-414.

Goulet, F., Hélie, P., & Vachon, P. (2010). Eugenol anesthesia in African clawed frogs (Xenopus laevis) of different body weights. Journal of the American Association for Laboratory Animal Science: JAALAS, 49(4), 460–463.

Gressler, L. T., Heinzmann, B. M., & Baldisserotto, B. (2021). Analgesia, anesthesia, and euthanasia of aquatic animals. Aquaculture Pharmacology, [S.L.], Elsevier, p. 297-346. Elsevier. http://dx.doi.org/10.1016/b978-0-12-821339-1.00007-6.

Grush, J. , Noakes, D. L. G. , & Moccia, R. D. (2004).The efficacy of clove oil as an anesthetic for the zebrafish, Danio rerio (Hamilton). Zebrafish,1(1), 46-53. https://doi.org/10.1089/154585404774101671

Huang, Q., Li, F., Liu, X., Li, W., Shi, W., Liu, F. F., O'Sullivan, B., He, Z., Peng, Y., Tan, A. C., Zhou, L., Shen, J., Han, G., Wang, X. J., Thorburn, J., Thorburn, A., Jimeno, A., Raben, D., Bedford, J. S., & Li, C. Y. (2011). Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nature medicine, 17(7), 860–866. https://doi.org/10.1038/nm.2385

Hussain, A., Brahmbhatt, K., Priyani, A., Ahmed, M., Rizvi, T. A., & Sharma, C. (2011). Eugenol Enhances the Chemotherapeutic Potential of Gemcitabine and Induces Anticarcinogenic and Anti-inflammatory Activity in Human Cervical Cancer Cells. Cancer Biotherapy And Radiopharmaceuticals, 26(5),519-527. http://dx.doi.org/10.1089/cbr.2010.0925

Hussain, A., Brahmbhatt, K. Priyani, A., Ahmed, M., Rizvi, T. A., & Sharma, C. (2011). Eugenol Enhances the Chemotherapeutic Potential of Gemcitabine and Induces Anticarcinogenic and Anti-inflammatory Activity in Human Cervical Cancer Cells. Cancer Biotherapy And Radiopharmaceuticals, 26(5),519-527. http://dx.doi.org/10.1089/cbr.2010.0925.

Islam, S. S., & Aboussekhra, A. (2019). Sequential combination of cisplatin with eugenol targets ovarian cancer stem cells through the Notch-Hes1 signalling pathway. Journal of Experimental & Clinical Cancer Research, 38(382),1–14. http://dx.doi.org/10.1186/s13046-019-1360-3

Jaganathan, S. K., Mondhe, D., Wani, Z. A., Pal, H. C., & Mandal, M. (2010). Effect of Honey and Eugenol on Ehrlich Ascites and Solid Carcinoma. Journal Of Biomedicine And Biotechnology1-5. http://dx.doi.org/10.1155/2010/989163.

Jiang, M., Qi, L., Li, L. & Li, Y. (2020). The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discovery. 6 (112), 2-11. https://doi.org/10.1038/s41420-020-00349-0

Kelly, K., Cochran, B. H., Stiles, C. D., & Leder, P. (1983). Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth fator.Cell, 35(1), 603-10.

Lagunin, A., Zakharov, A., Filimonov, D., & Poroikov, V. (2011). QSAR Modelling of Rat Acute Toxicity on the Basis of PASS Prediction. Molecular informatics, 30(2-3), 241–250. https://doi.org/10.1002/minf.201000151.

Leve, F., Morgado Díaz, J. A. (2012). Rho GTPase signaling in the develop ment of colorectal cancer. Journal of Cellular Biochemistry, 113(1), 2549 2559. https://doi.org/10.1002/jcb.24153

Liang, W. Z., Chou, C. T., Hsu, S. S., Liao, W. C., Shieh, P., Kuo, D. H., Tseng, H. W., Kuo, C. C., Jan, C. R. (2015). The involvement of mitochondrial apoptotic pathway in eugenol-induced cell death in human glioblastoma cells. Toxicology Letters, 232(1),122-132. http://dx.doi.org/10.1016/j.toxlet.2014.10.023.

Lutfi, M. , & Roque, N. F. (2014). Eugenias Histories. Química Nova na Escola, 36 (4),252-260. Http://dx.doi.org/10.5935/0104-8899.20140030.

Ma, M., Ma, Y., Zhang, G., Liao, R., Jiang, X., & Yan, X. (2017). Eugenol alleviated breast precancerous lesions through HER2 / PI3K-AKT pathway-induced cell apoptosis and S-phase arrest. Oncotarget, 8(34), 56296–310. Https://doi.org/10.18632/oncotarget.17626.

Manikandan, P., Murugan, R. S., Priyadarsini, R. V., Vinothini, G., & Nagini, S. (2010). Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG. Life sciences, 86(25-26), 936–941. https://doi.org/10.1016/j.lfs.2010.04.010

Marcu, K. B., Bossone, S. A., & Patel, A. J. (1992). Myc function and regulation. Annual Review Biochemisty, 61(1), 806-60.

Meloche,S., & Pouysségur, J.(2007). “TheERK1/2mitogen activatedproteinki nase pathway as a máster regulator of the G1 to S phase transition”. Oncogene, 26(1), 3227 3239. http://dx.doi.org/10.1038/sj.onc.1210414.

Mitani, K. (2001). Disease-related gene and tumor progression. Nippon Rinsho, 59(1), 2316- 2321.

NTP-National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). (1992).Le National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

Olayioye, M. A, Neve, R. M, Lane, H. A, & Hynes, N. E. (2000) .The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO Jornal, 19(1), 3159-67. Http://dx.doi.org/10.1093/emboj/19.13.3159.

Palsson, B. (2000). The challenges of in silico biology. Nature Biotechnology, 18 (1), 1147-1150. Http://dx.doi.org/10.1038/81125.

Paoli, S., Giani, S. T., Presta, S. P., Giani, T. S., Presta, G. A., Marcia Oliveira Pereira, M. O., Fonseca, A. S., Neto, J. B., Medeiros, A. C., Filho, S. D. S., &Filho, M. B.(2007). Effects of clove (Caryophyllus aromaticus L.) on the labeling of blood constituents with technetium-99m and on the morphology of red blood cells. Brazilian Archives of Biology and Technology, 50(spe), 175-182. https://dx.doi.org/10.1590/S1516-89132007000600022.

Parasuraman, S. (2011).Toxicological screening. Journal of Pharmacology & Pharmacotherapeutics , 2(2),74-79. Https://doi.org/ 10.4103/0976-500X.81895.

Rahman, M. F. , Haykal, M. N. , Siagian, N. A. Sriepindonnta, P. M. , & Tampubolon, N. A. (2018). Synthesis and Proapoptotic Activity on Cervical Cancer Cell of Ester Eugenol 1-(3-Methoxy-4-hydroxy)phenyl-2-propylmethanoate. Iop Conference Series: Materials Science and Engineering, 299(1),1-7. http://dx.doi.org/10.1088/1757-899x/299/1/012071.

Roque, M. L. N. F.(2014). Histórias de Eugênias. Química e Sociedade, 36 (1), 252–260.Http://dx.doi.org/10.5935/0104-889920140030.

Rothenstein, A. S., Booman, K. A., Dorsky, J., Kohrman, K. A., Schwoeppe, E. A., & Sedlak, R. I. (1983). Steltenkamp. Eugenol and clove leaf oil. A survey of consumer patchtest sensitization. Food and Chemical Toxicology, 21(1), 727-733. http://dx.doi.org/10.1016/0278-6915(83)90204-1

Ruttkies, C., Schymanski, E. L., Wolf, S., Hollender, J, & Steffen, N. (2016). MetFrag relaunched: incorporating strategies beyond in silico fragmentation. Journal of Cheminformatic, 8(3) .Https://doi.org/10.1186/s13321-016-0115-9

Scarff, R. & Torloni, F. (1968). Histological typing of breast tumors. International histological classification of tumors. Geneva: World Health Organization. http://dx.doi.org/10.1093/ajcp/78.6.806

Scherer, R., Wagner, R., Duarte, M. C. T., & Godoy, H. T. (2009). Composição e atividades antioxidante e antimicrobiana dos óleos essenciais de cravo-da-índia, citronela e palmarosa. Revista brasileira plantas medicinais,11(.4), 442-449. Http://dx.doi.org/10.1590/S1516-05722009000400013

Sotomayor, M., & Schulten, K. (2007). Single-Molecule Experiments in Vitro and in Silico. American Association for the Advancement of Science (AAAS). Science, 316 (582), 1144-1148. http://dx.doi.org/10.1126/science.1137591.

Srinivas, N., Sandeep, K. S., Anusha, Y., & Devendra, B. N. (2014). In Vitro Cytotoxic Evaluation and Detoxification of Monocrotaline (Mct) Alkaloid: An In Silico Approach. Journal of Biochemistry and Bioinformatics, 2(3).20-29.

Toft D. J., & Cryns V. L. (2011). Minireview: Basal-Like Breast Cancer: From Molecular Profiles to Targeted Therapies. Molecular Endocrinology, 25(2), 199- 211. http://dx.doi.org/ 10.1210/me.2010-0164.

Wingate D. (1989). Martindale: The extra pharmacopeia (29th ed). Gut, 30(12), 1804.Vidal, Lvo.(2008).Eugenol como anestésico para tilápia do Nilo. Pesquisa Agropecuária Brasileira, 43(8), 1069-1074. http://dx.doi.org/10.1590/S0100-204X2008000800017

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10/04/2021

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OLIVEIRA, N. S. .; ARRUDA, E. L. . Estudos In silico sobre as atividades anticancerígenas do Eugenol presente no Cravo Da Índia (Syzygium aromaticum). Research, Society and Development, [S. l.], v. 10, n. 4, p. e27910414165, 2021. DOI: 10.33448/rsd-v10i4.14165. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/14165. Acesso em: 24 nov. 2024.

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Ciências Educacionais