Diante dos resultados obtidos neste estudo, pode-se concluir que o OE apresenta relevante atividade anticâncer in vitro e in vivo, sendo que os mecanismos implicados nos seus efeitos citotóxicos incluem a interrupção do ciclo celular na fase G1 e a indução de morte
celular por apoptose, com participação da ativação de caspases.
57
58
REFERÊNCIAS
ABUKHDEIR, A.M.; PARK, B. H.. p21 and p27:roles in carcinogenesis and drug resistance.
Expert Reviews in Molecular Medicine, 2008.
ADAMS, R.P. Identification of Essential Oil Components by Gas Chromatography/Mass
Spectrometry, 4.ed. Allured Publishing Corporation, IL. 2007.
AGRA, M.F.; FREITAS, P.F.; BARBOSA-FILHO, J.M. Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil. Revista Brasileira de Farmacognosia, v. 17, n. 1, p. 114–140, 2007.
ALBUQUERQUE, C.C.; CAMARA, T.R.; MARIANO, R.L.R.; WILLADINO, L.; JUNIOR, C. M.; ULISSES, C. Antimicrobial Action of Essential Oil of Lippia gracilis Shauer,
Brazilian Archives of Biology and Technology, v. 49, n.4, p. 527-535, 2006.
ALBUQUERQUE, U.P.; MEDEIROS, P.M.; ALMEIDA, A.L.S.; MONTEIRO, J.M.; LINS NETO, E.M.F.; MELO, J.G.; SANTOS, J.P. Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: a quantitative approach. Journal Ethnopharmacology, v. 114, p. 325–354, 2007.
ALMEIDA, V.L.; LEITÃO, A.; REINA, L.D.C. B; MONTANARI, C.A.; DONNICI, C.L. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não
específicos que interagem com o DNA: uma introdução. Química Nova, v. 28, p. 118-129, 2005.
AMERICAN CANCER SOCIETY. The History of Cancer, 2012. Disponível em: <http://www.cancer.org>. Acesso em: 03/2013.
AMERICAN CANCER SOCIETY. Cancer Facts & Figures 2013. Atlanta: American Cancer Society, 2013.
BALUNAS, M.J.; KINGHORN, D. Drug discovery from medicinal plants. Life Sciences, v. 78, p. 431 – 441, 2005.
BAKKALI, F.; AVERBECK, S.; AVERBECK, D.; IDAOMAR, M. Biological effects of essential oils: a review. Food and Chemical Toxicology, v. 46, p. 446-475, 2008.
59 BERTHOLD, F. Isolation of human monocytes by ficoll density gradient centrifugation. Blut, v. 43, p. 67-371, 1981.
BEZERRA, D.P. Potencial anticâncer da plipartina e da piperina, aminas isoladas de
plantas do gênero piper, 2005. 140f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará-UFC, Fortaleza-Ceará.
BEZERRA, D.P.; CASTRO, F.O.; ALVES, A.P.N.N.; PESSOA, C.; MORAES, M.O.; SILVEIRA, E.R.; LIMA, M.A.S.; ELMIRO, F.J.M.; COSTA-LOTUFO, L.V. In vivo growth- inhibition of sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper.
Brazilian Journal of Medical and Biological Research, v. 39, p. 801-807, 2006.
BEZERRA, D.P.; PESSOA, C.; MORAES, M.O.; ALENCAR, N.M.; MESQUITA, R.O.; LIMA, M.W.; ALVES, A.P.; PESSOA, O.D.; CHAVES, J.H.; SILVEIRA, E.R.; COSTA- LOTUFO, L.V. In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species. Journal of Applied toxicology, v. 28, p. 599-607, 2008.
BITU, V.; BOTELHO, A.M.; COSTA, J.G.M.; RODRIGUES, F.F.G.; VERAS, H.N.H.; MARTINS, K.T.; LYRA, A.; COLUCHI, G.G.; RUELA, R.S.; QUEIROZ, D.B.;
SIQUEIRA, J.S.; QUINTANS-JUNIOR, L.J. Phythochemical screening and antimicrobial activity of essential oil from Lippia gracillis. Revista Brasileira de Farmacognosia, v. 22, p. 69-75, 2012.
BOURGAUD, F.;GRAVOT, A.; MILESE, S.; GONTIER, E. Producion of plant secondary matabolites: a historial perspective. Plant Science, v. 161, p. 839 – 851, 2001.
BRANDÃO, H. N.; DAVID, J. P.; COUTO, R. D.; NASCIMENTO, J. A. P.; DAVID, J. M. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Revista
Química Nova, p. 1359-1369, 2010.
BRITTO, A.C.S.; OLIVEIRA, A.C.A.; HENRIQUES, R.M.; CARDOSO, G.M.B.;
BOMFIM, D.S.; CARVALHO, A.A.; MORAES, M.O.; PESSOA, C.; PINHEIRO, M.L.B.; COSTA, E.V.; BEZERRA, D.P. In vitro and in vivo antitumor effects of the essential oil from the leaves of Guatteria friesiana. Planta Medica. v. 78, p. 409-414, 2012.
BROWN, M.G.; LAWCE, H.J. Peripheral blood cytogenetic methods. In: Barch, M.J., Knutsen, T., Spurbeck, J.L. (Eds.). The AGT Cytogenetics Laboratory Manual. Lippincott- Raven Publishers, Philadelphia, p.77-171, 1997.
60 BRUIN, E.C.; MEDEMA, J. P. Apoptosis and non-apoptotic deaths in cancer
development and treatment response. Cancer Treatment Reviews, v. 34, p. 737– 749, 2008.
CICENAS, J. ; VALIUS, M. The CDK inhibitors in cancer research and therapy. Journal of Cancer Research and Clinical Oncology, v.137, p. 1409-1418, 2011.
COSTA, S.M.O.; LEMOS, T.L.G.; PESSOA, O.D.L.; PESSOA, C.; MONTENEGRO, R.C.; BRAZ-FILHOS, R. Chemical Constituents from Lippia sidoides and Cytotoxic Activity.
Journal of Natural Products, v. 64, p. 792-795, 2001.
COTREAU, R.; KUTCHAN, T.M.; LEWIS, N.G. Natural products (Secundary Metabolites). In: BUCHANAN, B.; GRUISSEM, W.; JONES, R. (Eds). Biochemistry & Molecular
Biology of Plants, American Society of Plant Physiologists, 2000.
CRAGG, G.M.; NEWMAN, D.J. Antineoplastic agents from natural sources: achievements and future directions. Expert Opinion on Investigational Drugs, v.9, p.2783 – 2797, 2000.
CRAGG, G.M.; NEWMAN, D.J. Drug from nature: past achievements future prospects. In: IWU & WOOTTON (eds.), Ethnomedicine and Drug Discovery, Elsevier, 2002, 15p.
CRAGG, G.M.; NEWMAN, D.J. Plants as a source of anti-cancer agents. Journal of
Ethnopharmacology, v.100, p.72 – 79, 2005.
CRAGG, D.; NEWMAN, D. J. Natural products: A continuing source of novel drug leads.
Biochimica et Biophysica Acta, 2013. in press.
CROKER, A.K.; ALLAN, A.L. Cancer Stem Cells: Implications for the progression and treatment of metastatic disease. Journal of Cellular and Molecular Medicine, v.12, p.374 - 390, 2008.
CRUZ, E.M.O.; COSTA-JUNIOR, L.M.; PINTO, J.A.O.; SANTOS, D.A.; ARAUJO, S. A.; ARRIGONI-BLANK, M.F., BACCI, L., ALVES, P.B.; CAVALCANTI,S.C.H.; BLANK, A. F. Acaricidal activity of Lippia gracilis essential oil and its major constituents on the tick
Rhipicephalus (Boophilus) microplus. Veterinary Parasitology, 2013. in press
DEB, D.D.; PARIMALA, G.; SARAVANA; DEVI, S.; CHAKRABORTY, T. Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60. Chemico- Biological Interactions, v. 193, p. 97-106, 2011.
61 DEGTEREV, A., BOYCE, M.; YUAN. J.; A decade of caspases. Oncogene, v. 22, p. 8543– 8567, 2003.
DÖLL-BOSCARDIN, P.M.; SARTORATTO, A.; MAIA, B.H.; PAULA,
J.P.; NAKASHIMA, T.; FARAGO, P.V.; KANUNFRE, C.C. In vitro cytotoxic potential of essential oils of Eucalyptus benthamii and its related terpenes on tumor cell lines. Evidence-
Based Complementary and Alternative Medicine, ID 342652, 2012.
EKHOLM, S.V.; REED, S.I.Regulation of G1 cyclin-dependent kinases in the mammalian cell cycle. Current Opinion in Cell Biology, V.12, p. 676–684. 2000.
ELISABETSKY, E., COSTA-CAMPOS, L. Medicinal plant genetic resources and
international cooperation: the Brazilian perspective. Journal of Ethnopharmacology. v. 51, p. 111–20, 1996.
ELMORE, S. Apoptosis: A review of Programmed Cell Death. Toxicology Pathology, v. 35, p. 495-516, 2007.
ENDERS, G.H. Mammalian Interphase Cdks: Dispensable Master Regulators of the Cell Cycle, Genes & Cancer, v. 3, n. 11-12, p. 614-618, 2012.
FERREIRA, G.C.; EPPING, M.; KRUYT, F.A.E.; GIACCONE, G. Apoptosis: Target of Cancer Therapy. Clinical Cancer Research, v. 8, p. 2024-234, 2002.
FULDA, S.; DEBATIN, K-M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, v. 25, p. 4798–4811, 2006.
GALLORINI, M.CATALDI, A.; DI GIACOMO, V. Cyclin-dependent kinase modulators and cancer therapy. BioDrugs. v. 26, n. 6, 2012.
GARRETT, M.D. Cell cycle control and cancer. Current Science, v. 81, n. 5, 2001.
GOMES, S.V.F. Desenvolvimento de método por Cromatografia Líquida de Alta
Eficiência para diferenciação de genótipos de Lippia gracilis Shauer.2009. 163f.
Dissertação (Mestrado em Quimica)- Universidade Federal de Sergipe, São Cristóvão, 2009.
GRIFFITHS, M.; SUNDARAM, H. Drug design and testing: profiling of antiproliferative agents for cancer therapy using a cell-based methyl-[3H]-thymidine incorporation assay.
62 GRIVICICH, I.; REGNER,A.; ROCHA A. B. Morte cellular por apoptose. Revista
Brasileira de Cancerologia, v. 53, n. 3, p. 335-343, 2007.
GUILHON, C.C.; RAYMUNDO, L.J.; ALVIANO, D.S.; BLANK, A.F.; ARRIGONI- BLANK, M.F.; MATHEUS, M.E.; CAVALCANTI, S.C.; ALVIANO, C.S.; FERNANDES, P.D. Characterisation of the anti-inflammatory and antinociceptive activities and the
mechanism of the action of Lippia gracilis essential oil. Journal of Ethnopharmacology, v. 135, p. 406-413, 2011.
GUIMARÃES, A.G.; GOMES, S.V.; MORAES, V.R.; NOGUEIRA, P.C.; FERREIRA, A.G.; BLANK, A.F.; SANTOS, A.D.; VIANA, M.D.; SILVA, G.H.; QUINTANS, JÚNIOR, L.J. Phytochemical characterization and antinociceptive effect of Lippia gracilis Schauer.
Journal of Natural Medicines, v. 66, p. 428-434, 2011.
HANAHAN, D.; WEINGERG, R.A. The hallmarks of cancer. Cell, v.100, p.57 – 70, 2000.
HANAHAN, D.; WEINGERG, R.A. Hallmarks of cancer: The Next Generation. Cell, v.144, p.646 – 674, 2011.
INCA, Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Fisiopatologia do câncer, Rio de Janeiro, p. 29, 2006.
INCA, Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Coordenação Geral de Ações Estratégicas.
Coordenação de Prevenção e Vigilância de Câncer. Estimativas 2012: Incidência de Câncer
no Brasil. Rio de Janeiro, p.26, 2011a.
INCA, Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. ABC do câncer: abordagens básicas para o controle
do câncer. Rio de Janeiro, p. 128, 2011b.
INCA, Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Quimioterapia. Disponível em:
<http://www.inca.gov.br/conteudo_view.asp?id=101>. Acesso em: 03/2013.
JOHNSON, D.G.; WALKER, C.L. Cyclins and cell cycle checkpoints. Annual Review of
63 KATZUNG, G.B. Basic and Clinical Pharmacology, 11th edn., McGraw-Hill Medical, United States of America, 2010.
KERR, J.F.R.; WILLIE, A.H.; CURRIE, A. R.; Apoptosis: A basic biological phenomenon with wideranging implications in tissue kinetics. British Journal of Cancer, v. 26, p. 239- 257, 1972.
KERR, J.F.R. History of the events leading to the formulation of the apoptosis concept.
Toxicology, v. 181 - 182, p. 471 - 474, 2002.
KINGSTON, D.G.I. Recent advances in the chemistry of taxol. Journal of Natural
Products, v.63, p.726 - 734, 2000.
KUMMAR, V.; ABBAS, A.; FAUSTO, N.; ROBBINS, S.L.; COTRAN, R.S. Pathology
Basis of Disease, 8. ed. China: WB Saunders, 2010.
KURASHIGE, S.; MITSUHASHI, S. Macrophage activities in sarcoma 180-bearing mice and EL4-bearing mice. Gann, v.73, p.85 – 90, 1982.
LI, F.; TIEDE, B.; MASSAGUÉ, J.; KANG, Y. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Research, v. 17, p. 3-14, 2007.
LHEUREUX, S; LE MOULEC, S. Molecules involved in apoptosis regulation as therapeutic targets in oncology. Bull Cancer. v.98, n. 9, p. 1029- 1036, 2011.
LORENZI, H.; MATOS, F.J.A. Plantas Medicinais no Brasil: Nativas e Exóticas, 2. ed. Nova Odessa: Instituto Plantarum, , 2008.
MAREK, L. The role of the apoptosome in the activation of procaspase-9. Postepy Hig Med
Dosw, v.67, p. 54-64, 2013.
MALUMBRES, M. Cyclins and related kinases in cancer cells. Journal of BUON, v. 12, suplemento 1, p. 45-52, 2007.
MCDONALD, E.R.; EL-DEIRY, W.S. Cell cycle control as a basis for cancer drug development (Review). International Journal of Oncology, v.16, n. 5, p. 871-886, 2000.
64 MCGAHON, A.J.; MARTIN, S.J.; BISSONNETTE, R.P.; MAHBOUBI, A.; SHI, Y.;
MOGIL, R.J.; NISHIOKA, W.K.; GREEN, D.R. The end of the (cell) line: methods for the study of apoptosis in vitro. Methods in Cell Biology, v. 46, p. 153-185, 1995.
MEERAN, S.M.; KATIYAR, S. K. Cell cycle control as a basis for cancer chemoprevention through dietary agents. Front Bioscience, v. 13, p. 2191-2202, 2008.
MENDES, S.S.; BOMFIM, R.R.; JESUS, H.C.; ALVES, P.B.; BLANK, A.F.; ESTEVAM, C.S.; ANTONIOLLI, A.R.; THOMAZZI, S.M. Evaluation of the analgesic and anti-
inflammatory effects of the essential oil of Lippia gracilis leaves. Journal of
Ethnopharmacology, v. 129, p. 391-397, 2010.
MESA-ARANGO, A.C.; MONTIEL-RAMOS, J.; ZAPATA, B.; DURÁN, C.; BETANCUR- GALVIS, L.; STASHENKO, E. Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity.
Memórias do Instituto Oswaldo Cruz, Rio de janeiro, v. 104, n. 6, p. 878-884, 2009.
MORAES M.O.; FONTELES, M.C.; MORAES, M.E.A. Screening for anticancer activity of plants from the Northeast of Brazil. Fitoterapia LXVIII, n. 3, p. 235–239, 1997.
MORI, S.A.; SILVA, L.A.M.; LISBOA, G.; CORADIN, L. Manual de manejo do herbário
fanerogâmico, 2.ed., Ilhéus: CEPLAC, 1989.
MORIN,X.; BELLAICHE, Y. Mitotic Spindle Orientation in Asymmetric and Symmetric Cell Divisions during Animal Development, Developmental Cell, v. 21, 2011.
MORGAN, D.O. Cyclin-dependent kinases: Engines, Clocks e Microprocessors. Annual
Review of Cell and Developmental Biology. v. 13, p. 261-291, 1997.
MUSGROVE, E.A.; CALDON, C.E.; BARRACLOUGH, J.; STONE, A.; SUTHERLAND, R. L. Cyclin D as a therapeutic target in cancer,Nature Reviews Cancer, v.11, p. 558-572,
2011.
NETO, R.M.; MATOS, F.J.A.; ANDRADE, V.S.; MELO, M.C.N.; CARVALHO, C.B.M.; GUIMARÃES, S.B.; PESSOA, O.D.L.; SILVA, S.L.; SILVA, S.F.R.; VASCONCELOS, P.R.L. The essential oil from Lippiagracilis Schauer, Verbenaceae, in diabetic rats. Revista
65 NEVES, I.A.; DE OLIVEIRA, J.C.S.; DA CAMARA, C.A.G.; SCHWARTZ, M.O.E.
Chemical composition of the leaf oils of Lippia gracilis Schauer from two localities of Pernambuco. Journal of Essential OilResearch, v. 20, p. 157-160, 2008.
NEWMAN, D.J.; CRAGG, G.M.; SNADER, K.M. The influence of natural products upon drug discovery. Natural Product Reports, v.17, p.215 – 234, 2000.
NEWMAN, D.J.; CRAGG, G.M.; SNADER, K.M. Natural products as sources of new drugs over the period 1981-2002. Journal of Natural Products, v.66, p.1022 – 1037, 2003.
NEWMAN, D.J.; CRAGG, G.M.; Natural products as sources of new drugs over the 1586 30 years from 1981 to 2010, Journal of Natural Products. v. 75, p. 311–338, 2012.
NICOLETTI, I.; MAGLIORATI, G.; PAGLIACCI, M.C.; GRIGNANI, F.; RICCARDI, C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. Journal of Immunological Methods, v. 139, p. 271-279, 1991.
NICHOLSON, D. W. From bench to clinic with apoptosis-based therapeutic agents, Nature, v. 407, p. 810-816, 2000.
NORBURY, C.; NURSE, P. Animal cell cycles and their control. Annual Review of
Biochemistry, v. 61, p. 441-468, 1992.
OECD Environmental Health and Safety Publications, Guidance Document on the
Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for experimental animals used in safety evaluation environmental health and safety monograph series on testing and assessment (No 19), Paris, 2000.
OLIVEIRA, D.R.; LEITÃO, G.G.; BIZZO,T.T.;LOPES, D.; ALVIANO, D. S.;ALVIANO, C.S.; LEITÃO, S. G. Chemical and antimicrobial analyses of oil of Lippia origanoides HBK.
Food Chemistry, v. 101, p. 236-240, 2007.
OLIVEIRA, O. R.; TERAO, D.; CARVALHO, A. C. P. P.; INNECCO,R.; C.
ALBUQUERQUE, C. Effect of essential oil from genus Lippia plants over the control of fungi contaminants on the micro propagation of plants. Revista Ciências Agronômicas, v. 39, n. 1, p. 94-100, 2008.
OKADA, H.; MAK, T.W.; Pathways of apoptotic and non-apoptotic death in tumor cells.
66 PASCUAL, M.E.; SLOWING, K.; CARRETERO, E.; SÁNCHEZ MATA, D.; VILLAR, A.
Lippia: traditional uses, chemistry and pharmacology: a review. Journal of
Ethnopharmacology, v. 76, p. 201–214, 2001.
PEREIRA, A. C. R. L.; OLIVEIRA, J.V.; GONDIM JUNIOR, M. G. C.; CÂMARA, C. A.G. Atividade inseticida de óleos essenciais e fixos sobre Callosobruchus maculatus (FABR., 1775) (Coleoptera: Bruchidae) em grãos de caupi [Vigna unguiculata (L.) WALP. Ciência e
Agrotecnologia, v. 32, n. 3, p. 717-724, 2008.
PESSOA, C.; SILVEIRA, E.R.; LEMOS, T.L.; WETMORE, L.A.; MORAES, M.O.; LEYVA, A. Antiproliferative effects of compounds derived from plants of Northeast Brazil. Phytotherapy Research, v. 14, p.187-191, 2000.
PESSOA, O.D., DE CARVALHO, C.B., SILVESTRE, J.O., LIMA, M.C., NETO, R.M., MATOS, F.J., LEMOS, T.L. Antibacterial activity of the essential oil from Lippia aff. gracillis. Fitoterapia, v. 76, p. 712-714, 2005.
PESSOA, C. COSTA-LOTUFO, L.V.; LEYVA, A.; MORAES, M.E.A.; MORAES, M.O. Anticancer potencial of Northeast Brasilian Plants. In: KHAN, M.T.H.; ATHER, A. (eds.).
Lead Molecules from Natural Products, Elsevier, 2006, 15p.
PINTO, A.C.; SILVA, D.H.S.; BOLZANI, V.S.; LOPES, N.P.; EPIFANIO, R.A. Produtos naturais: atualidade, desafios e perspectivas. Química Nova, v.25, p.45 -61, 2002.
PUCCI, B.; KASTEN, M.; GIORDANO, A. Cell cycle and apoptosis. Neoplasia, v. 2, p. 291-299, 2000.
RANG, H.P.; DALE, M.M.; RITTER, J.M.; FLOWER, R.J.; HENDERSON, G.
Farmacologia. 7. ed.,Elsevier, 2012.
RIBEIRO S.S.; JESUS, A.M.; ANJOS, C.S.; SILVA, T.B.; SANTOS, A.D.C.; JESUS, J.R.; ANDRADE, M.S.; SAMPAIO, T.S.; GOMES, W.F.; ALVES, P.B.; CARVALHO, A.A.; PESSOA, C.; MORAES, M.O.; PINHEIRO, M.L.B.; PRATA, A.P.N.; BLANK, A.F.; SILVA-MANN, R.; MORAES, V.R.S.; COSTA, E.V.; NOGUEIRA, P.C.L.; BEZERRA, D.P. Evaluation of the cytotoxic activity of some Brazilian medicinal plants. Planta Medica, v.78, p. 1601-1606, 2012.
ROCHA, A.B.; LOPES, R.M.; SCHWARTSMANN, G. Natural products in anticancer therapy. Currente. Opinion in Pharmacology, v. 1, p. 364-369, 2001.
67 ROWINSKY, E. The Vinca Alkaloids. KUFE, D.W.; POLLOCK, R.E.; WEICHSELBAUM, R.R. et al., (Eds.), Holland-Frei Cancer Medicine. 6. ed. th, Hamilton (ON): BC DECKER, 2003.
SAELENS X.; FESTJENS, N.; WALLE, L.V.; GURP, M.V.; LOO, G.V.;
VANDENABEELE, P. Toxic proteins released from mitochondria in cell death. Oncogene, v. 23, p. 2861–2874, 2004.
SAMPIERI, K.; FODDE, R. Cancer stem cell and metastasis. Seminars in Cancer Biology, v.22, p. 187-193, 2012.
SANTOS, A.S.; ALVES, S.M.; FIGUEIREDO, F.J.C.; ROCHA NETO, O. G. Descrição de Sistemas e de Métodos de Extração de óleos Essenciais e Determinação de Umidade de Biomassa em Laboratório, Comunicado técnico 99 do Ministério da Agricultura, Ecologia
e Abastecimento, 2004.
SANTOS, J.S.; MELO, J. I. M.; ABREU, M. C.; SALES, M.F. Verbenaceae sensu stricto na região de xingó: Alagoas e Sergipe, Brasil, Rodriguésia, v. 60, n. 4, p. 985-998, 2009.
SANTOS, M.M. Caspases como alvo terapêutico para o tratamento de doenças neurodegenerativas. Química121, 2011.
SENDEROWICZ, A. M. Cyclin-dependent kinases as new targets for theprevention and treatment of cancer. Hematology Oncology Clinics of North America, v.16, p. 1229-1253, 2002.
SENDEROWICZ, A. M. Targeting cell cycle and apoptosis for the treatment of human malignancies. Current Opinion in Cell Biology, v. 16, p. 670-678, 2004.
SILVA, W.J.; DÓRIA, G.A.; MAIA, R.T.; NUNES, R.S.; CARVALHO, G.A.; BLANK, A.F.; ALVES, P.B.; MARÇAL, R.M.; CAVALCANTI, S.C. Effects of essential oils on
Aedes aegypti larvae: alternatives to environmentally safe insecticides. Bioresource
Technology-Journal, v. 99, p. 3251-3255, 2008.
STONE, A.; SUTHERLAND, R.L. MUSGROVE, E.A. Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics. Critical Reviews in
Oncogenesis, v.17, n. 2, p. 175-198, 2012.
68 SUFFNESS, M.; PEZZUTO, J.M. Assays related to cancer drug discovery. In: Hostettmann, K. (Editor). Methods in Plant Biochemistry: Assays for Bioactivity. London: Academic Press, p. 71–133, 1990.
TALMADGE, J.E.; FILDLER, I.J. AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective. Cancer Research, v. 70, n. 14, p. 5649-5669, 2010.
TELES, T.V.; BOMFIM, R.R.; ALVES, P.B.; BLANK, A.F.; JESUS, H.C.R.; QUINTANS- JR., L.J.; SERAFINI, M.R.; BONJARDIM, L.R.; ARAÚJO, A.A.S. Composition and evaluation of the lethality of Lippia gracilis essential oil to adults of Biomphalaria glabrata
and larvae of Artemia salina. African Journal Biotechnology, v. 9, p. 8800-8804, 2010.
TERBANCHÉ, F.C.; KORNELIUS, G. Essential oil constituents of the genus Lippia (Verbenaceae) – A literature review. Journal of Essential Oil Research, v. 8, p. 471-485, 1996.
TRET'YAKOV, K.V., Retention Data. In: Linstrom, P.J, Mallard, W.G. (Eds.). NIST
Chemistry Webbok, NIST Standard Reference Database Number 69, National Institute of
Standards and Technology, Gaithersburg, MD, 2008.Disponível em: <http://webbook.nist.gov/chemistry/>, acesso em : Setembro, 2012.
THONEL, A. ERIKSSON, J.E. Regulation of death receptors—Relevance in cancer therapies. Toxicology and Applied Pharmacology, v. 207, p. 123-132, 2005.
VAN DEN DOOL, H.; KRATZ, P.D. A generalization of the retention index system including linear temperature programmed gas-liquid partition chromatography. Journal
Chromatography A, v. 11, p. 463-471. 1963.
VERMEULEN, K.; BERNEMAN, Z.N.; BOCKSTAELE, D.R.V. Cell cycle and apoptosis.
Cell Proliferation, v. 36, p. 165-175, 2003.
VERPOORTE, R.; MARASCHIN, M. Engenharia do metabolismo de Plantas Medicinais. In: Yunes RA; Calixto JB. (Org.). Plantas Medicinais sob a Ótica da Química Medicinal
Moderna. Chapecó: /UNOESC, v. 1, p. 381-432, 2001.
VIALLARD, J.F.; LACOMBE, F.; BELLOC, F.; PELLEGRIN, J.L.; REIFFERS, J. Molecular mechanisms controlling the oil cycle: fundamental aspects and implications for oncology. Cancer Radiotherapy, v. 5, n. 2, 2001.
69 WALSH, C.M.; EDINGER, A.L. The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis. Immunological Reviews, v. 236, p. 95–109, 2010.
WARFEL, N.A.; EL-DEIRY, W.S. p21WAF1 and tumourigenesis: 20 years after. Current
Opinion in Oncology, v. 25, 2013.
World Health Organization (WHO). Library cataloguing-in-Publication Data. Global status
report on noncommunicable diseases 2010.
World Health Organization. Cancer (WHO). Fact sheet n° 297. Feb 2011. [homepage on the internet]. Geneva: World Health Organization; Disponível em: <
http://www.who.int/mediacentre/factsheets/fs297/en/ >. Acesso em: 11 de março de 2013.
WÜRSTLE, M. L.; LAUSSMANN, M. A.; REHM, M. The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the
apoptosome. Experimental Cell Research, 2012. in press.
ZHANG J.T. New drugs derived from medicinal plants. Therapie, v. 57, n. 2, p. 137–150, 2002.
ZIMMERMANN, K. C.; BONZON, C.; GREEN, D. R. The machinery of programmed cell death. Pharmacology & Therapeutics, v.92, p. 57-70, 2001.
ZOUBIRI, S.; BAALIOUAMER, A. Potentiality of plants as source of insecticide principles.
Jornal of Saudi Chemical Society, 2011.
ZUCKERBERG, C. Ultrastructure of Sarcoma 180. Cancer Research, v.33, p.2278 - 2282, 1973.
71
APÊNDICE
72
73 ANEXO A- Declaração do Comitê de Ética e Pesquisa com Animais para a
74 ANEXO B- Declaração do Comitê de Ética e Pesquisa com Animais