Produtos Naturais e a Apoptose: Um Enfoque Promissor para a Descoberta de Novos Fármacos

S. S. Costa; M. F. Muzitano

doi:10.32712/2446-4775.2006.52

Produtos Naturais e a Apoptose: Um Enfoque Promissor para a Descoberta de Novos Fármacos

v. 2 n. 02 (2006)
46-53
16/10/2013
01/09/2006
https://doi.org/10.32712/2446-4775.2006.52

S. S. Costa
M. F. Muzitano

Palavras-chave

Resumo

A morte celular programada, denominada apoptose celular, faz parte de diversos processos vitais, dentre os quais podemos citar o desenvolvimento embrionário, o controle de tumores e a regulação de populações de células do sistema imune. Distúrbios na regulação da apoptose estão envolvidos em uma variedade de doenças, tais como a Síndrome da Imunodeficiência Adquirida (AIDS), o câncer, a doença de Alzheimer, o mal de Parkinson e as doenças auto-imunes. Hoje há acesso a estudos bastante aprofundados sobre moléculas que atuam diretamente em alvos terapêuticos nos mecanismos apoptóticos e que, por esta razão, poderiam ser utilizadas no tratamento de várias doenças ainda sem cura. Os trabalhos mais promissores nesta área focalizam, por exemplo, substâncias isoladas do alho (Allium sativum), terpenos de Caseria membranaceae e de Zingiber mioga, além de alguns produtos do ácido gambógico, isolado de Garcinia hurburyi. Muitos esforços têm sido empregados visando aplicar moléculas capazes de induzir a apoptose no tratamento do câncer, entretanto são poucos os trabalhos direcionados a outras doenças. Esta revisão tem como objetivo principal mostrar o potencial de moléculas de origem natural para o tratamento do câncer e dessas outras patologias, com base nos mais conhecidos alvos terapêuticos envolvidos na apoptose.

Referências

CHAKRABARTY, S.; ROY, M.; HAZRA, B.; BHATTACHARYA, R.K. Induction of apoptosis in human cancer cell lines by diospyrin, a plant-derived bisnaphthoquinonoid, and its synthetic derivatives. Cancer Letters, v.188, n.1-2, 85-93, 2002.
CHAN, S-L; LEE, M.C.; TAN, K.O.; YANG, L-K; LEE, A.S.Y.; FLOTOW, H.; FU, N.Y.; BUTLER, M.S.; SOEJARTO, D.D.; BUSS, A.D.; YU, V.C. Identification of chelerythrine as an inhibitor of BclXL function. The Journal of Biological Chemistry, v.278, n.23, p.20453-20456, 2003.
CHIU, L.C.M.; WAN, J.M.F. Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of bcl-2 expression. Cancer Letters, v.145, 17-27, 1999.
CHOI, J.; CONRAD, C.C.; MALAKOWSKY, C.A.; TALENT, J.M.; YUAN, C-S; GRACY, R.W. Flavones from Scutellaria baicalensis Georgi attenuate apoptosis and protein oxidation in neuronal cell lines. Biochimica et Biophysica Acta, v.1571, p.201- 210, 2002.
DIRSCH, V.M.; GERBES, A.L.; VOLLMAR, A.M. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappa B. Molecular Pharmacology, v.53, n.3, p.402-407, 1998.
FERNANDES, J.; WEINLICH, R.; CASTILHO, R.O.; KAPLAN, M.A.C.; AMARANTE-MENDES, G.P.; GATTASS, C.R. Pomolic acid triggers mitochondria-dependent apoptotic cell death in leukemia cell line. Cancer Letters, v.219, n.1, p.49-55, 2005.
HERMAN-ANTOSIEWICZ, A.; SINGH, S.V. Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review. Mutation Research, v.555, p.121-131, 2004.
HORTA, M.F.; YOUNG, J.D.-E. Apoptose: quando a célula programa 1999.
HUANG, D.-M.; SHEN, Y.-C.; WU, C.; HUANG, Y.-T.; KUNG, F.-L.; TENG, C.-M.; GUH, J.-H. Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane diterpenoids in human prostate cancer PC-3 cells. European Journal of Pharmacology, v.503, p.17-24, 2004.
KEUM, Y.-S.; KIM, J.; LEE, K.H.; PARK, K.K.; SURH, Y.-J.; LEE, J.M.; LEE, S.-S., YOON, J.H.; JOO, S.Y.; CHA, I.H.;
YOOK, J.I. Induction of apoptosis and caspase-3 activation by chemopreventive [6]-paradol and structurally related compounds in KB cells. Cancer Letters, v.177, n.1, p.41-47, 2002.
KITADA, S.; LEONE, M.; SARETH, S.; ZHAI, D.; REED, J.C.; PELLECCHIA, M. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting b-cell lymphocyte/leukemia-2 proteins. Journal of Medicinal Chemistry, v.46, p.4259-4264, 2003.
LEUNG, H.W.-C.; WU, C.-H.; LIN, C.-H.; LEE, H.-Z. Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis. European Journal of Pharmacology, v.508, n.1-3, p.77-83, 2005.
LIU, D.; HUANG, Z. Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis. Apoptosis, v.6, n.6, p.453-462, 2001.
LU, H.F.; SUE, C.C.; YU, C.S.; CHEN, S.C.; CHEN, G.W.; CHUNG, J.G. Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food and Chemical Toxicology, v.42, n.10, p.1543-1552, 2004.
LUO, Y.; SMITH, J.V.; PARAMASIVAM, V.; BURDICK, A.; CURRY, K.J.; BUFORD, J.P.; KHAN, I.; NETZER, W.J.; XU, H.; BUTKO, P. Inhibition of amyloid-â aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proceedings of the National Academy of Sciences of the United States of America, v.99, n.19, p.12197-12202, 2002.
McCONKEY, D.J. Biochemical Determinants of Apoptosis and Necrosis. Toxicology letters, v.99, p.157-168, 1998.
MELNIKOVA, I.; GOLDEN, J. Apoptosis-targeting therapies. Nature Reviews. Drug Discovery, v.3, p.905-906, 2004.
MIYOSHI, N.; NAKAMURA, Y.; UEDA, Y.; ABE, M.; OZAWA, Y.; UCHIDA, K.; OSAWA, T. Dietary ginger constituents, galanals A and B, are potent apoptosis inducers in Human T lymphoma Jurkat cells. Cancer Letters, v.199, n.2, p.113-119, 2003.
NEWMAN, D.J.; CRAGG, G.M.; SNADER, K.M. Natural products as sources of a new drugs over the period 1981-2002. Journal of Natural Products, v.66, p.1022-1037, 2003
NICHOLSON, D.W. From bench to clinic with apoptosis-based therapeutic agents. Nature, v.407, p.810-816, 2000.
OOMMEN, S.; ANTO, R.J.; SRINIVAS, G.; KARUNAGARAN, D. Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. European Journal of Pharmacology, v.485, n.1-3, p.97- 103, 2004.
REED, J.C. Apoptosis-based therapies. Nature Reviews. Drug Discovery, v.1, p.111-121, 2002.
SCHROETER, H.; SPENCER, J.P.E.; RICE-EVANS, C.; WILLIAMS, R.J. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochemical Journal, v.358, p.547-557, 2001.
ZHANG, H.-Z.; KASIBHATLA, S.; WANG, Y.; HERICH, J.; GUASTELLA, J.; TSENG, B.; DREWE, J.; CAI, S.X. Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay. Bioorganic & Medicinal Chemistry, v.12, v.2, p.309-317, 2004.
ZHOU, H.-B.; ZHU, J.-R. Paclitaxel induces apoptosis in human gastric carcinoma cells. World Gastroenterology, v.9, n.3, p.442-445, 2003.

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Autor(es)

S. S. Costa
Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, NPPN-UFRJ, 21941-590 Rio de Janeiro, RJ, Brasil
M. F. Muzitano
Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, NPPN-UFRJ, 21941-590 Rio de Janeiro, RJ, Brasil

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Produtos Naturais e a Apoptose: Um Enfoque Promissor para a Descoberta de Novos Fármacos. Rev Fitos [Internet]. 1º de setembro de 2006 [citado 22º de novembro de 2024];2(02):46-53. Disponível em: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/52

Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

[1] CHAKRABARTY, S.; ROY, M.; HAZRA, B.; BHATTACHARYA, R.K. Induction of apoptosis in human cancer cell lines by diospyrin, a plant-derived bisnaphthoquinonoid, and its synthetic derivatives. Cancer Letters, v.188, n.1-2, 85-93, 2002.

[2] CHAN, S-L; LEE, M.C.; TAN, K.O.; YANG, L-K; LEE, A.S.Y.; FLOTOW, H.; FU, N.Y.; BUTLER, M.S.; SOEJARTO, D.D.; BUSS, A.D.; YU, V.C. Identification of chelerythrine as an inhibitor of BclXL function. The Journal of Biological Chemistry, v.278, n.23, p.20453-20456, 2003.

[3] CHIU, L.C.M.; WAN, J.M.F. Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of bcl-2 expression. Cancer Letters, v.145, 17-27, 1999.

[4] CHOI, J.; CONRAD, C.C.; MALAKOWSKY, C.A.; TALENT, J.M.; YUAN, C-S; GRACY, R.W. Flavones from Scutellaria baicalensis Georgi attenuate apoptosis and protein oxidation in neuronal cell lines. Biochimica et Biophysica Acta, v.1571, p.201- 210, 2002.

[5] DIRSCH, V.M.; GERBES, A.L.; VOLLMAR, A.M. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappa B. Molecular Pharmacology, v.53, n.3, p.402-407, 1998.

[6] FERNANDES, J.; WEINLICH, R.; CASTILHO, R.O.; KAPLAN, M.A.C.; AMARANTE-MENDES, G.P.; GATTASS, C.R. Pomolic acid triggers mitochondria-dependent apoptotic cell death in leukemia cell line. Cancer Letters, v.219, n.1, p.49-55, 2005.

[7] HERMAN-ANTOSIEWICZ, A.; SINGH, S.V. Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review. Mutation Research, v.555, p.121-131, 2004.

[8] HORTA, M.F.; YOUNG, J.D.-E. Apoptose: quando a célula programa 1999.

[9] HUANG, D.-M.; SHEN, Y.-C.; WU, C.; HUANG, Y.-T.; KUNG, F.-L.; TENG, C.-M.; GUH, J.-H. Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane diterpenoids in human prostate cancer PC-3 cells. European Journal of Pharmacology, v.503, p.17-24, 2004.

[10] KEUM, Y.-S.; KIM, J.; LEE, K.H.; PARK, K.K.; SURH, Y.-J.; LEE, J.M.; LEE, S.-S., YOON, J.H.; JOO, S.Y.; CHA, I.H.;

[11] YOOK, J.I. Induction of apoptosis and caspase-3 activation by chemopreventive [6]-paradol and structurally related compounds in KB cells. Cancer Letters, v.177, n.1, p.41-47, 2002.

[12] KITADA, S.; LEONE, M.; SARETH, S.; ZHAI, D.; REED, J.C.; PELLECCHIA, M. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting b-cell lymphocyte/leukemia-2 proteins. Journal of Medicinal Chemistry, v.46, p.4259-4264, 2003.

[13] LEUNG, H.W.-C.; WU, C.-H.; LIN, C.-H.; LEE, H.-Z. Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis. European Journal of Pharmacology, v.508, n.1-3, p.77-83, 2005.

[14] LIU, D.; HUANG, Z. Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis. Apoptosis, v.6, n.6, p.453-462, 2001.

[15] LU, H.F.; SUE, C.C.; YU, C.S.; CHEN, S.C.; CHEN, G.W.; CHUNG, J.G. Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food and Chemical Toxicology, v.42, n.10, p.1543-1552, 2004.

[16] LUO, Y.; SMITH, J.V.; PARAMASIVAM, V.; BURDICK, A.; CURRY, K.J.; BUFORD, J.P.; KHAN, I.; NETZER, W.J.; XU, H.; BUTKO, P. Inhibition of amyloid-â aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proceedings of the National Academy of Sciences of the United States of America, v.99, n.19, p.12197-12202, 2002.

[17] McCONKEY, D.J. Biochemical Determinants of Apoptosis and Necrosis. Toxicology letters, v.99, p.157-168, 1998.

[18] MELNIKOVA, I.; GOLDEN, J. Apoptosis-targeting therapies. Nature Reviews. Drug Discovery, v.3, p.905-906, 2004.

[19] MIYOSHI, N.; NAKAMURA, Y.; UEDA, Y.; ABE, M.; OZAWA, Y.; UCHIDA, K.; OSAWA, T. Dietary ginger constituents, galanals A and B, are potent apoptosis inducers in Human T lymphoma Jurkat cells. Cancer Letters, v.199, n.2, p.113-119, 2003.

[20] NEWMAN, D.J.; CRAGG, G.M.; SNADER, K.M. Natural products as sources of a new drugs over the period 1981-2002. Journal of Natural Products, v.66, p.1022-1037, 2003

[21] NICHOLSON, D.W. From bench to clinic with apoptosis-based therapeutic agents. Nature, v.407, p.810-816, 2000.

[22] OOMMEN, S.; ANTO, R.J.; SRINIVAS, G.; KARUNAGARAN, D. Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. European Journal of Pharmacology, v.485, n.1-3, p.97- 103, 2004.

[23] REED, J.C. Apoptosis-based therapies. Nature Reviews. Drug Discovery, v.1, p.111-121, 2002.

[24] SCHROETER, H.; SPENCER, J.P.E.; RICE-EVANS, C.; WILLIAMS, R.J. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochemical Journal, v.358, p.547-557, 2001.

[25] ZHANG, H.-Z.; KASIBHATLA, S.; WANG, Y.; HERICH, J.; GUASTELLA, J.; TSENG, B.; DREWE, J.; CAI, S.X. Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay. Bioorganic & Medicinal Chemistry, v.12, v.2, p.309-317, 2004.

[26] ZHOU, H.-B.; ZHU, J.-R. Paclitaxel induces apoptosis in human gastric carcinoma cells. World Gastroenterology, v.9, n.3, p.442-445, 2003.