DSpace logo

Use este identificador para citar ou linkar para este item: http://repositorioinstitucional.uea.edu.br//handle/riuea/4121
Registro completo de metadados
Campo DCValorIdioma
dc.contributor.authorOliveira, Regiane Costa de-
dc.date.available2022-08-10-
dc.date.available2022-08-11T16:57:27Z-
dc.date.issued2020-07-10-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4121-
dc.description.abstractHematological neoplasms are a heterogeneous group of diseases originating in the bone marrow that present as main tumors of lymphoid and hematopoietic tissues leukemias, lymphomas and myelomas. The main current treatments include chemotherapy and radiation therapy. However, most of these treatments are expensive and result in intense side effects for patients, which demands new safer and more cost-effective therapeutic alternatives. The purpose of this study was to investigate the in vitro anticancer and imunomodulatory activities of natural and semi-synthetic compounds against hematological neoplasms. As human normal peripheral blood mononucleated cells (PBMC) was used in the assays, this project was duly approved by the Research Ethics Committee (CEP) of the HEMOAM Foundation, according to the guidelines recommended by the resolution 466/2012 of the Ministry of Health. First, PBMC and Vero cells were treated with different concentrations of the following compounds: Br- Ell-S03Na, pyrazoloisoquinoline, Z1 and Z2. The cytotoxicity was assessed using the K562, HL-60 and U937 cell lines. All substances tested showed anticancer activity, without significant cytotoxic effect against non-cancerous cells. The substance that showed the best anticancer activity was a derivative of zerumbone (Z1) that had an IC50 value of 5.20μM in HL-60 cells. Regarding the cell cycle, it was observed that the substances Z1 and pyrazoloisoquinoline induced greater capture of cells in the G1 phase of the cell cycle, while in relation to the substance Br-Ell-S03Na and Z2, a higher proportion of capture was observed in the S and G2 phases, respectively. The substances Br-Ell-S03Na and pyrazoloisoquinoline induced the expression of IL-6, but inhibited the expression of IL-8. The Z2 substance also inhibited the expression of IL-8. The results presented by this study demonstrate that the analyzed substances have an important anticancer and immunomodulatory potential, which make them possible candidates to be explored in prospective in vivo studiespt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectFitoterápicospt_BR
dc.subjectLeucemiaspt_BR
dc.subjectNeoplasiaspt_BR
dc.subjectBioprospecçãopt_BR
dc.titleAvaliação in vitro da atividade anticancerígena de compostos naturais e semissintéticos contra neoplasias hematológicaspt_BR
dc.title.alternativeIn vitro evaluation of the anticancer activity of natural and semi-synthetic compounds against hematological neoplasmspt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-11T16:57:27Z-
dc.contributor.advisor1Pontes, Gemilson Soares-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/9081671233815990pt_BR
dc.contributor.referee1Costa, Allysom Guimarães da-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/7531662673281014pt_BR
dc.contributor.referee2Sartim, Marco Aurélio-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/0196692401515816pt_BR
dc.contributor.referee3Campos, Ceci Sales-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/9752987836124768pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/2804370054665763pt_BR
dc.description.resumoAs neoplasias hematológicas são um grupo heterogêneo de doenças originadas na medula óssea que apresentam como principais tumores de tecidos linfoides e hematopoiéticos as leucemias, linfomas e mielomas. Os principais tratamentos atuais incluem quimioterápicos e radioterapia. Contudo, a maioria destes tratamentos é de alto custo e resulta em intensos efeitos colaterais aos pacientes, o que demanda novas alternativas terapêuticas mais seguras e de melhor custo-benefício. Este estudo teve como objetivo principal investigar a atividade anticancerígena e imunomoduladora in vitro de compostos naturais e semissintéticos contra neoplasias hematológicas. Como foram utilizadas células mononucleadas normais do sangue periférico (PBMC) humanas, este projeto foi devidamente aprovado pelo Comitê de Ética em Pesquisa (CEP) da Fundação HEMOAM, de acordo com as diretrizes preconizadas pela resolução 466/2012 do Ministério da Saúde. Primeiramente, PBMC e células Vero foram tratadas com diferentes concentrações dos seguintes compostos: Br-Ell-S03Na, pirazoloisoquinolina, Z1 e Z2. A avaliação da citotoxicidade foi realizada por meio do teste MTT. Em seguida, foi investigada as atividades anticancerígena e imunomoduladora utilizando-se as linhagens celulares K562, HL-60 e U937.Todas as substâncias testadas apresentaram atividade anticancerígena, sem efeito citotóxico significativo contra células não cancerígenas. A substância que apresentou melhor atividade anticancerígena foi um derivado de zerumbona (Z1) que apresentou valor de IC50 de 5.20μM em células HL-60. Em relação ao ciclo celular, foi observado que as substâncias Z1 e pirazoloisoquinolina induziram maior captura na fase G1 do ciclo celular, enquanto que as substâncias Br-Ell-S03Na e Z2 foi observado uma maior a proporção de captura na fase S e G2, respectivamente. As substâncias Br-Ell-S03Na e pirazoloisoquinolina induziram a expressão de IL-6, porém inibiram a expressão de IL- 8. A substancia Z2 também inibiu a expressão de IL-8. Os resultados apresentados por este estudo demonstram que as substâncias analisadas apresentam importante potencial anticancerígeno e imunomodulador, os que as tornam possíveis candidatas para serem exploradas em estudos prospectivos in vivopt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
dc.relation.references47 19. Prakash O, Kumar A, Kumar P, Ajeet. Anticancer Potential of Plants and Natural Products: A Review. American Journal of Pharmacological Sciences. v. 1, n. 6, 104-115, 2013. 20. Yokosuka A., Haraguchi M., Usui T., Kazami S., Osada H., Yamori T., Mimaki Y. & Glaziovianin A. Bioorg. Med. Chem. Lett., 17(11), 3091-3094, 2007. 21. Bhuiyan, N.I; Chowdhury, J.U.; Begum, J. Chemical investigation of the leaf and rhizome essential oils of Zingiber zerumbet (L.) Smith from Bangladesh,” Bangladesh Journal of Pharmacology. 4: 9-12, 2009. 22. Lisana, T. Tumores sólidos e neoplasias hematológicas. Sobre Câncer. Rev Bras Hematol Hemoter. v.28, n.1, 2010. 23. Khatami M. Unresolved inflammation: immune tsunami or erosion of integrity in immune- privileged and immune-responsive tissues and acute and chronic inflammatory diseases or câncer. Expert Opin Biol Ther. 11 (11): 1419-1432, 2011. 24. Brasil. Ministério da Saúde; Instituto Nacional do Câncer. Tipos de câncer [Internet]. Rio de Janeiro; 2010. 25. Vardiman JW. et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 114(5):937- 51, 2009. 26. Chisesi, T. State of the art in the treatment of CLL. Rev. Bras. Hematol. Hemoter. v.31, s.2, p. 51-56, 2009. 27. Silva S, Ávila FD, Soares Mo Perfil Hematológico e Bioquímico Sérico de Pacientes Submetidas à Quimioterapia Antineoplasica. Revista de Enfermagem e Atenção à Saúde, v. 2, n. 02, 2013. 28. Instituto Nacional de Câncer José Alencar Gomes da Silva. Coordenação Geral de Ações Estratégicas, Coordenação de Prevenção e Vigilância, Área de Vigilância do Câncer relacionado ao Trabalho e ao Ambiente. Rio de Janeiro: INCA, 2012. 187 p. 29. Merino, A. Clasificación de las leucemias agudas mieloidesAcute myeloid leukemia classification. Rev Lab Clín. v3, i3, p139-147, 2010. 30. Monteiro TAF, Arnaud MVC, Barros VLS, Monteiro JLF, Vasconcelos PFC. Identificação do Gene EBER1 e EBNA1 do vírus Epstein Barr (EBV) em tecidos de pacientes com doença de Hodgkin na região Norte do Brasil. Rev Panam Infectol. 2014;16(1):17-24. 31. Diehl V. Chemotherapy or combined modality treatment: the optimal treatment for Hodgkin's disease. J Clin Oncol. 2004 Jan; 22:15-8. 32. Ministério da Saúde (BR). Secretaria Nacional de Assistência à Saúde. Instituto Nacional de Câncer. Câncer no Brasil: dados dos registros de câncer de base populacional. Rio de Janeiro: INCA; 2011. 33. Kasper DL, Braunwald E, Fauci AS, et al. Harrison’s Principles of Internal Medicine. 17a ed. New York: McGraw-Hill Medical Publishing Division; 2008. 34. Campos LC, de Andrade DAP. Linfoma não-Hodgkin de células do manto: relato de caso. Rev. Med. Minas Gerais 2009; 19(2): 177-179. 48 35. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol [Internet]. Elsevier; 2014 Nov 1 [cited 2018 Mar 26];15(12): e538-48. 36. Nikhil C. Munshi; Dan L. Longo; Kenneth C. Anderson. Plasma Cell Disorders. In: Harrison’s Principles of Internal Medicine, 19e. 2015. 37. World Health Organization. Global Action plan for the prevention and control of noncommunicable diseases 2013-2020. Geneva, 2013. 38. Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, Genève, v. 136, n. 5, p. 359-386, 2015. 39. Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, Hoboken, v. 68, n. 6, p. 394-424, Nov. 2018. 40. Ferlay, J. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International journal of cancer, New York, v. 144, n. 8, p. 19411953, Apr. 2019. 41. Instituto Nacional de Câncer José Alencar Gomes da Silva/ Ministério da Saúde. Estimativa de câncer no Brasil. 2020. Disponível em: http://www1.inca.gov.br/estimativa/2020/estimativa- 2020.pdf. 42. Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer. A situação do câncer no Brasil/Ministério da Saúde, Secretaria de Atenção à Saúde, Instituto Nacional de Câncer, Coordenação de Prevenção e Vigilância. -Rio de Janeiro: INCA, 2016. 43. World Health Organization (WHO). International Agency for Research on Cancer. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. World; 2016b. 44. International Myeloma Foundation (IMF). Concise Review of the Disease and Treatment Options: Multiple Myeloma. 2012. Disponível em: https://doi. org/10.1007/978-1-4614-8520-9. Acesso em: 13 de março de 2019. 45. Almeida TJB. Avanços e perspectivas para o diagnóstico da leucemia linfoide aguda. Cand Rev Virt, v.5, n.1, p.40-55, 2009. 46. Barbosa CMPL. Manifestações músculo-esqueléticas como apresentação inicial das leucemias agudas na infância. Sociedade Brasileira de Pediatria, Jornal de Pediatria, v. 78, n.6, p. 481 a 484, 2002. 47. Farias MG, Castro SM. Diagnóstico laboratorial das leucemias linfoides agudas. J. Bras. Patol. Med. Lab. v.40, n.2, p.91-8, 2014. 48. Fadel AP. Investigação laboratorial de LLA. Ac&T Científica, v. 1, n. 2, 2010. 49. Dantas GKS et al. Diagnóstico diferencial da leucemia linfoide aguda em pacientes infantojuvenis. Rev Un Val Rio Verde, Três Corações, v.13, n.2, p. 3-18, 2015. 49 50. Silva GC et al. Diagnóstico Laboratorial das leucemias mielóides agudas. Jorn Bras Pat Med Lab. v.42, n.2, p.77-84, 2007. 51. Moreira CA; Okamoto OK. Medicina genômica e prática clínica. Einstein, São Paulo, v. 2, n. 3, p. 235-236, 2015. 52. Armitage JO How I treat patients with diffuse large B-cell lymphomas. Blood. 2007;110(1):29- 36 53. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with RCHOP. Blood. 2007; 109(5):1857-61 54. Fundação Internacional de Mieloma (2019). Diagnóstico do Mieloma. Disponível em <http://www.myeloma.org.br/diagnostico.php> Acesso em fevereiro de 2019. 55. Almeida, V. L. et al. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução. Química Nova. v. 28, n. 1, p. 118- 129, 2005. 56. Amos, T. A.; Gordon, M. Y. Sources of human hematopoietic stem cells for transplantation-a review. Cell Transplantation. v. 4, n. 6, p. 547-69, 2005. 57. Meesat R. et al. Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose. Proceedings of the National Academy of Sciences, 109(38), E2508-E2513, 2012. 58. Instituto Nacional De Câncer (Brasil). ABC do câncer: abordagens básicas para o controle do câncer / Instituto Nacional de Câncer. – Rio de Janeiro: Inca. p128, 2011. 59. Guerard, E. J; Bishop M. R. Overview of Non-Hodgkin’s Lymphoma, 2012. 60. Hajjaji, N; Bougnoux, P. Selective sensitization of tumors to chemotherapy by marine-derived lipids: a review. Cancer Treat Rev. v.39 n. 5, p. 473-88, 2012. 61. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5(3), 161– 171, 2005. 62. Mukherjee S, Patra CR. Biologically synthesized metal nanoparticles: recent advancement and future perspectives in cancer theranostics. Future Sci. OA 3(3), FSO203, 2017. 63. Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer. A situação do câncer no Brasil/Ministério da Saúde, Secretaria de Atenção à Saúde, Instituto Nacional de Câncer, Coordenação de Prevenção e Vigilância. -Rio de Janeiro: INCA, 2016. 64. Lee S, Margolin K. Cytokines in cancer immunotherapy. Cancers (Basel). 2011;3(4):3856–93. 65. Germano G, Allavena P, Mantovani A. Cytokines as a key component of cancer-related inflammation. Cytokine. 2008; 43:374-379 66. Capece D, Verzella D, Tessitore A, Alesse E, Capalbo C, Zazzeroni F. Cancer secretome and inflammation: The bright and the dark sides of NF-κB. Semin Cell Dev Biol [Internet]. 2018;78:51–61. Available from: http://dx.doi.org/10.1016/j.semcdb.2017.08.004. 50 67. Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004. 68. Sektioglu IM, Carretero R, Bulbuc N, Bald T, Tüting T, Rudensky AY, et al. Basophils promote tumor rejection via chemotaxis and infiltration of CD8+ T cells. Cancer Res. 2017. 69. Schwartz C, O’Grady K, Lavelle EC, Fallon PG. Interleukin 33: An innate alarm for adaptive responses beyond Th2 immunity-emerging roles in obesity, intestinal inflammation, and cancer. Eur J Immunol. 2016. 70. Setrerrahmane S, Xu H. Tumor-related interleukins: Old validated targets for new anti-cancer drug development. Molecular Cancer. 2017. 71. Lippitz BE, Harris RA. Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis. Oncoimmunology [Internet]. 2016;5(5):1–12. Available from: http://dx.doi.org/10.1080/2162402X.2015.1093722. 72. Mauer J, Denson JL, Brüning JC. Versatile functions for IL-6 in metabolism and cancer. Trends Immunol. 2015;36(2):92–101. 73. Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008;26:453. 74. Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485. 75. Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose Interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003;21:3127–32. 76. Brat DJ, Bellail AC, Van Meir EG. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 2005;7(2):122–33. 77. Hidaka H, Ishiko T, Furuhashi T, Kamohara H, Suzuki S, Miyazaki M, et al. Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface: Impact on human pancreatic carcinoma cell growth by autocrine regulation. Cancer. 2002;95(6):1206–14. 78. Ahmad N, Ammar A, Storr SJ, Green AR, Rakha E, Ellis IO, et al. IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunol Immunother [Internet]. 2018;67(4):537–49. Available from: http://dx.doi.org/10.1007/s00262-017-2106-8 79. Joshi BH, Leland P, Lababidi S, Varrichio F, Puri RK. Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease. Cancer Med. 2014 80. Ostrand R S, Grusby MJ, Clements VK. Cutting Edge: STAT6-Deficient Mice Have Enhanced Tumor Immunity to Primary and Metastatic Mammary Carcinoma. J Immunol. 2000. 81. Chang Y, Zhang M, Jiang Y, Liu Y, Luo H, Hao C, et al. Preclinical and clinical studies of coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Discov Med. 2017. 82. Blagodatski A, Yatsunskaya M, Mikhailova V, Tiasto V, Kagansky A, Katanaev VL.Medicinal 51 mushrooms as an attractive new source of natural compounds for future cancer therapy. Oncotarget. 2018;9(49):29259–74. 83. Newell DR. Como desenvolver um can- sucesso cer droga - moléculas para medicamentos ou alvos para tratamentos. Eur J Cancer. 41: 676-82, 2005. 84. Garland Cf, Mohr, SB, Gorham Ed, Grant WB, Garland FC. Roleof ultravioleta B irradianceand vitamin D in prevention of ovaria cancer. Am Prev Med. 31: 512-4, 2006. 85. Buyru N. Tezol A, Yosunkaya-Fenerci E, Dalay N Vitamin D receptor gene polymorphism in breast câncer. Exp mol. Med. 35: 550-5, 2003. 86. Liu Y, Tian J, Qian K, Zhao XB, Susan LM, yang L. Recent progress on c-4 modified Podophillo toxina an log as potent antitumor agents. Med Rev. 35: 1-62, 2015. 87. Ay Sun A. Simonyi Q. Wang, e G. Sun, “Beyond the paradoxo francês: proteção dos polifenóis de uva contra processos rodegenerative neu-” Alcoholism: Clinical & Experimental Research, vol. 28, 2004. 88. Varoni EM, Faro AFL, Shariti-Rad J, Iriti M. Anticancer molecular mechanism of revesratrol. Front Nutr 2016; 3:8. 89. Mazumder A, Cerella C, Diederich M. Natural scaffolds in anticâncer therapy and precision medicine. Biotechnol Adv [Internet]. 2018;36(6):1563-85. 90. Wutthithamavet, W. Traditional Medicine, Odean Store Press, Bangkok, Thailand. 1997. 91. Sulaiman MR et al. Antinociceptive activity of the essential oil of Zingiber zerumbet. Planta Medica, 76: 107–112, 2010. 92. Yob, NJ et al. “Zingiber zerumbet (L.) Smith: A Review of Its Ethnomedicinal, Chemical, and Pharmacological Uses,” Evidence-Based Complementary and Alternative Medicine, 12, 2011. 93. Dai JR et al. Zerumbone, an HIV-inhibitory and cytotoxic sesquiterpene of Zingiber aromaticum and Z. zerumbet,” Natural Product Letters, vol. 10, no. 2, pp. 115–118, 1997. 94. Kim M et al. Zerumbone, a tropical ginger sesquiterpene, inhibits colon and lung carcinogenesis in mice,” International Journal of Cancer, vol. 124, no. 2, pp. 264–271, 2009. 95. Jalili-Nik M, Sadeghi MM, Mohtashami E, Mollazadeh H, Afshari AR, Sahebkar A. Zerumbone Promotes Cytotoxicity in Human Malignant Glioblastoma Cells through Reactive Oxygen Species (ROS) Generation. Oxid Med Cell Longev. 2020;2020. 96. Junior, JCM et al. A Citometria De Fluxo Como Instrumento De Avaliação Da Atividade Imunomodulatória De Extratos E Substâncias Isoladas De Plantas Medicinais. Revista Brasileira de Farmacognosia 16: 645-655, 2006. 97. Hashimoto Y. Thalidomide as a multi-template for development of biologically active compounds. Arch Pharm (Weinheim). 2008;341(9):536-47. 98. Brandão HN, David JP, Couto RD, Nascimento JAP, David JM. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Quim Nova. 2010;33(6): 1359-69. 52 99. Thakore P, Mani RK, Kavitha SJ. A brief review of plants having anti-cancer property. In J Pharm Res Dev 2012; 3: 129-36. 100. Sing S, Jarial R, Kanwar SS. Therapeutic effect herbal medicines on obesity: herbal pancreatic lipase innibitors. Wudpecker J Med Plants 2013; 2:53-65. 101. Khazir J, Mir BA, Pilcher L, Riley DL. Role of plants in anticancer drug discovery. Phytochem. Lett. 2014, 7, 173–181. 102. Almeida VL. d., A. Leitão, et al. (2005). "Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução." Química Nova 28: 118-129. 103. Ishikawa H, Seto D, Porino C, Tam P, Kakei H et al. Total Synthesis of Vinblastine, Vincristine, Related Natural Products, and Key Structural Analogues. J Am Chem Soc. Author manuscript; available in PMC 2010 April 8. 104. Li Y, Zhang T, Hasan K, Liu S, Lee HF, Neuman B, Yu Y, Clouthier SG, Steven J. Schwartz MSW and DS. NIH Public Access. Clin Cancer Res. 2010;23(1):1–19. 105. Liang J, Hänsch GM, Hübner K, Samstag Y. Sulforaphane as anticancer agent: A double- edged sword? Tricky balance between effects on tumor cells and immune cells. Adv Biol Regul [Internet]. 2019;71:79–87. 106. Sharma U, Kumar P, Kumar N, Singh B. Recent Advances in the Chemistry of Phthalimide Analogues and their Therapeutic Potential. Mini-Reviews Med Chem. 2010;10(8):678–704. 107. Zwergel C, Gaascht F, Valente S, Diederich M, Bagrel D, Kirsch G. Aurones: Interesting natural and synthetic compounds with emerging biological potential. Nat Prod Commun. 2012;7(3):389–94. 108. Hadjeri M, Barbier M, Ronot X, Mariotte AM, Boumendjel A, Boutonnat J. Modulation of P-glycoprotein-mediated multidrug resistance by flavonoid derivatives and analogues. J Med Chem. 2003;46(11):2125–31. 109. Schoepfer J, Fretz H, Chaudhuri B, Muller L, Seeber E, Meijer L, et al. Structure-based design and synthesis of 2-benzylidene-benzofuran-3-ones as flavopiridol mimics. J Med Chem. 2002;45(9):1741–7. 110. Sidney BY. ALKALOIDS Alkaloids of Ochrosia clliptica Labill .’. 1959;215(in 1955) 111. Fiona M. Deane, Charlotte M. Miller, Anita R. Maguire and FOM. Modifications to the Vilsmeier-Haack Formylation of 1,4- Dimethylcarbazole and Its Application to the Synthesis of Ellipticines. J Heterocycl Chem. 2011;48(July):814–23. 112. Kizek R, Adam V, Hrabeta J, Eckschlager T, Smutny S, Burda J V., et al. Anthracyclines and ellipticines as DNA-damaging anticancer drugs: Recent advances. Pharmacol Ther [Internet]. 2012;133(1):26–39. 113. Dodin G, Andrieux M, Kabbani H Al. Binding of ellipticine to P-lactoglobulin. 1990;700(1 990):697–700. 53 114. Ma W, Lu S, Pan P, Sadatmousavi P, Yuan Y, Chen P. Pharmacokinetics of Peptide Mediated Delivery of Anticancer Drug Ellipticine. PLoS One. 2012;7(8). 115. Hägg M, Berndtsson M, Mandic A, Zhou R, Shoshan MC, Linder S. Induction of endoplasmic reticulum stress by ellipticine plant alkaloids. Mol Cancer Ther. 2004;3(4):489–97. 116. Pradeep K. Dagur and J. Philip McCoy, Jr. Collection, Storage, and Preparation of Human Blood Cells.Curr Protoc Cytom. 2015; 73: 5.1.1–5.1.16. 117. Dhyani A, Machado-Neto JA, Favaro P, Saad ST. ANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth. Eur J Cancer. 2015 Jan;51(2):252-9. doi: 10.1016/j.ejca.2014.11.01. 118. Dantas, B.B et al. Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction. The Japanese Society of Pharmacognosy and Springer Japan 2015, doi: 10.1007/s11418-014-0881-5. 119. Yue GG1, Chan BC, Hon PM, Lee MY, Fung KP, Leung PC, Lau CB. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa. Food Chem Toxicol. 2010 Aug-Sep;48(8-9):2011-20. 120. Stiborová M, Poljaková J, Martínková E, Bořek-Dohalská L, Eckschlager T, Kizek R, et al. Ellipticine cytotoxicity to cancer cell lines-a comparative study. Interdiscip Toxicol. 2011;4(2):98–105. 121. Woodward RB, Iacobucci GA, Hochstein IA. The Synthesis of Ellipticine. J. Am. Chem. Soc. 1959, 81, 4434–4435. 122. Anderson G, Clavel M, Smyth J, Giaccone G, Gracia M, Planting AS, Dalesio O, Kirkpatrick A, McVie G. Phase II study of 9-hydroxy-2-methyl-ellipticinium acetate (ellipticinium) in patients with advanced carcinoma of the lung. Eur. J. Cancer Clin. Oncol. 1989, 25, 909–910. 123. Russell EG, Guo J, O’Sullivan EC, O’Driscoll CM, McCarthy FO, Cotter TG. 7-formyl-10- methylisoellipticine, a novel ellipticine derivative, induces mitochondrial reactive oxygen species (ROS) and shows anti-leukaemic activity in mice. Invest New Drugs. 2016;34(1):15– 23. 124. Shamsuzzaman, Asif M, Ali A, Mashrai A, Khanam H, Sherwani A, et al. Design, Synthesis and Biological Evaluation of Steroidal Tetrazoles as Antiproliferative and Antioxidant Agents. Eur Chem Bull. 2014;3 (11):1075–80. 125. Costa RGA, Anunciação TA d., Araujo M de S, Souza CA, Dias RB, Sales CBS, et al. In vitro and in vivo growth inhibition of human acute promyelocytic leukemia HL-60 cells by Guatteria megalophylla Diels (Annonaceae) leaf essential oil. Biomed Pharmacother [Internet]. 2020;122 (November 2019):109713. Available from: https://doi.org/10.1016/j.biopha.2019.109713. 126. Netto C D Silva, Salustiano A J, Bacelar E J, Riça T S, Cavalcante IG, M. C, & Costa P R. 2010. New Pterocarpanquinones: synthesis, antineoplasic activity on cultured human malignant cell lines and TNF-α modulation in human PBMC cells. Bioorganic & medicinal chemistry, 18(4), 1610-1616. 54 127. Murakami A, Ohigashi H, Ikeda Y, Kizaki M. a Fas- and mitochondria-mediated pathway. Cancer Sci [Internet]. 2007;98(1):2–10. Available from: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2006.00362.x 128. Sakinah et al. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell International 2007, 7:4 doi:10.1186/1475-2867-7-4. 129. Hoffman, L. Spetner, and M. Burke, “Redox-regulated mechanism may account for zerumbone’s ability to suppress cancer-cell proliferation,” Carcinogenesis, vol. 23, no. 11, pp. 1961-1962, 2002. 130. Liu C K, Shih T Y, Kuo C L et al., “Sulforaphane induces cell death through G2/M phase arrest and triggers apoptosis in HCT 116 human colon cancer cells,” The American Journal of Chinese Medicine, vol. 44, no. 6, pp. 1289–1310, 2016. 131. Monma H, Lida Y, Moritani T., et al., “Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in humanpancreatic cancercells,” PloS One, vol.13, no.3, article e0193990, 2018. 132. Kirana C, McIntosh GH, Record IR, Jones GP. Antitumor activity of extract of Zingiber aromaticum and its bioactive sesquiterpenoid zerumbone. Nutr Cancer. 2009;45(2):218–25. 133. Habli Z, Toumieh G, Fatfat M, Rahal ON, Gali-Muhtasib H. Emerging cytotoxic alkaloids in the battle against cancer: Overview of molecular mechanisms. Molecules. 2017;22(2):1–22. 134. Deane FM, O’Sullivan EC, Maguire AR, Gilbert J, Sakoff JA, McCluskey A et al (2013) Synthesis and evaluation of novel ellipticines as potential anti-cancer agents. Org Biomol Chem 11(8):1334–134. 135. Lerman LS (1961) Structural considerations in the interaction of DNA and acridines. J Mol Biol 3:18–30. 136. Prudent R, Moucadel V, Nguyen CH, Barette C, Schmidt F, Florent JC, Lafanechere L, Sautel CF, Duchemin-Pelletier E, Spreux E, Filhol O, Reiser JB, Cochet C (2010) Antitumor activity of pyridocarbazole and benzopyridoindole derivatives that inhibit protein kinase CK2. Cancer Res 70(23):9865–9874. 137. Shurin, M. Cancer as an immune-mediated disease. ImmunoTargetsTher. 2012, 1, 1–6. [CrossRef] [PubMed] 138. Wahid B, Ali A, Rafique S, Waqar M, Wasim M, Wahid K, Idrees M. An overview of cancer immunotherapeutic strategies. Immunotherapy 2018, 10, 999–1010. [CrossRef] [PubMed] 139. Ribas A, Wolchok J D. Cancer immunotherapy using checkpoint blockade. Science 2018, 359, 1350–1355. [CrossRef] [PubMed] 140. Weiden J, Tel J, Figdor C G. Synthetic immune niches for cancer immunotherapy. Nat. Rev. Immunol. 2018, 18, 2012–2019. [CrossRef] [PubMed] 141. Hegmans J.P.J.J, Aerts J.G.J.V. Immunomodulation in cancer. Curr. Opin. Pharmacol. 2014, 17, 17–21. [CrossRef 55 142. Mikucki ME, Fisher DT, Ku AW, Appenheimer MM, Muhitch JB, Evans SS. Preconditioningthermal therapy: Flipping the switch on IL-6 for anti-tumour immunity. Int. J. Hyperth. 2013, 29, 464–473. [CrossRef] [PubMed] 143. Fisher DT, Appenheimer MM, Evans SS. The two faces of IL-6 in the tumor microenvironment. Semin. Immunol. 2014, 26, 38–47. [CrossRef] 144. Rose-John, S. Il-6 trans-signaling via the soluble IL-6 receptor: Importance for the proinflammatory activities of IL-6. Int. J. Biol. Sci. 2012, 8, 1237–1247. [CrossRef]. 145. Grivennikov SI, Greten F R, Karin M. Immunity, Inflammation, and Cancer. Cell 2010, 140, 883–899. [CrossRef] 146. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science 2011, 331, 1565–1570. [CrossRef] 147. Aung TN, Qu Z, Kortschak RD, Adelson DL. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int J Mol Sci. 2017;18(3). 148. Michalak B, Piwowarski JP, Granica S, Waltenberger B, Atanasov AG, Khan SY, et al. Eupatoriopicrin inhibits pro-inflammatory functions of neutrophils via suppression of il-8 and tnf-Alpha production and p38 and erk 1/2 map kinases. J Nat Prod. 2019;82(2):375–85. 149. Robson RL, Westwick J, Brown Z. Interleukin-1-induced IL-8 and IL-6 gene expression and production in human mesangial cells is differentially regulated by cAMP. Kidney Int. 1995, 48, 1767–1777. 150. Gutiérrez M, Santamaría R, Gómez-Reyes JF, Guzmán HM, Ávila-Román J, Motilva V, et al. New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum Asbestinum. Mar Drugs. 2020; 151. Huang TT, Ojcius DM, Young JD, Wu YH, Ko YF, Wong TY, et al. The anti-tumorigenic mushroom agaricus blazei murill enhances IL-1β production and activates the NLRP3 inflammasome in human macrophages. PLoS One. 2012. 152. Raghuwanshi SK, Su Y, Singh V, Haynes K, Richmond A, Richardson RM. The Chemokine Receptors CXCR1 and CXCR2 Couple to Distinct G Protein-Coupled Receptor Kinases to Mediate and Regulate Leukocyte Functions. J. Immunol. 2012, 189, 2824–2832. 153. David JM, Dominguez C, Hamilton DH, Palena C. The IL-8/IL-8R axis: A double agent in tumor immune resistance. Vaccines. 2016. 154. Mosmann T R, Coffman R L.TH1 and TH2 cells: Different patterns of lymphokine secretion lead todifferent functional properties. Annu. Rev. Immunol. 1989, 7, 145–173. 155. Nishimura T, Iwakabe K, Sekimoto M, Ohmi Y, Yahata T, Nakui M, Sato T, Habu S, Tashiro H, Sato M.; et al. Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo. J. Exp. Med. 1999, 190, 617–627. [CrossRef] 156. Garbett N C, Graves D E. Extending nature’s leads: The anticancer agent ellipticine. Curr. Med. Chem. - Anti-Cancer Agents 2004, 149 –172pt_BR
dc.publisher.initialsUEApt_BR
Aparece nas coleções:DISSERTAÇÃO - PPCAH Programa de Pós-Graduação em Ciências Aplicadas à Hematologia

Arquivos associados a este item:
Arquivo Descrição TamanhoFormato 
Avaliação in vitro da atividade anticancerígena de compostos naturais e semissintéticos contra neoplasias hematológicas.pdf2,1 MBAdobe PDFVisualizar/Abrir
Mostrar registro simples do item Visualizar estatísticas


Os itens no repositório estão protegidos por copyright, com todos os direitos reservados, salvo quando é indicado o contrário.