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

Natural Products and Apoptosis: a Promising Approach for Drug Discovery

Vol. 2 No. 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

Keywords

Abstract

The programmed cell death, also called apoptosis, is part of several vital processes, as the embryonic development, the control of tumors and the regulation of populations of cells of the immune system. Disturbs of its regulation are involved with a variety of illnesses such as AIDS, cancer, Alzheimer's, autoimmune diseases and Parkinson's disease. Today we have access to several studies showing in a deep way the direct effect of molecules on therapeutic targets in apoptotic mechanisms that could be used in the treatment of some incurable illnesses. The most promising results in this area concern, for example, substances obtained from garlic (Allium sativum), terpenes from Caseria membranaceae and Zingiber mioga and derivatives of gambogic acid, isolated from Garcinia hurburyi. Many efforts have been made to apply apoptosis inducer drugs in cancer therapy, but few studies have been correlated to other illnesses. The aim of this review is to show the potential of natural molecules to the treatment of cancer and those other pathologies, based on the most studied apoptosis therapeutic targets.

References

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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Author(s)

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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Natural Products and Apoptosis: a Promising Approach for Drug Discovery. Rev Fitos [Internet]. 2006 Sep. 1 [cited 2024 Nov. 22];2(02):46-53. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/52

This work is licensed under a 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.