Natural Products in Advance Clinical Trials Applied to Cancer

M. V. N. Souza
A. C. Pinheiro
M. L. Ferreira
R. S. B. Gonçalves
Camilo H. da C. Lima

Keywords

Anti-neoplasic Activity
Anti-cancer Drugs
Drug Development

Abstract

Nowadays, natural products represent an outstanding source of compounds that play an important role in cancer treatment. Due to the importance of nature as a source of new cancer drugs candidates, the aim of this review is to highlight natural products, which are under clinical trials against this disease.

References

  1. AHN, Y. M.; VOGETI, L.; LIU, C.; SANTHAPURAM, H. K. R.; WHITE, J. M.; VASANDANI, V.; MITSCHER, L. A.; LUSHINGTON, G. H.; HANSON, P. R.; POWELL, D. R.; HIMES, R. H.; ROBY, K. F.; YE, Q.; GEORG, G. Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. Bioorganic & Medicinal Chemistry, v.15, n.2, p.702-713, 2007.
  2. ALBERTS, B.; BRAY, D.; LEWIS, J.; RAFF, M.; ROBERTS, K.; WATSON, J. D. Molecular biology of the cell, Garland Publishing; New York & London; 1994.
  3. ALBERTS, M. W.; WILLIAMS, R.T.; BROWN, E. J.; TANAKA, A.; HALL, F. L.; SCHREIBER, S. L. FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line. Journal of Biological chemistry, v.268, n.30, p.22825-22829, 1993.
  4. ALCARO, S.; MARINO, T.; ORTUSO, F.; RUSSO, N. Conformational behavior of antineoplastic peptides Dolastatin 10 and Dolastatin 15 from Monte Carlo and molecular dynamics simulations. International Journal of Quantum Chemistry, v.107, n.2, p.318-325, 2007.
  5. BAI, X.C.; LIU, AN-LING, LUO, SHEN-QIU. Phospholipase C is required for survival in heat stress: involvement of protein kinase C-dependent Bcl-2 phosphorylation. Journal of Biochemistry, v.131, n.2, p.207-212, 2002.
  6. BAGATELL, R.; BELIAKOFF, J.; DAVID, C. L.; MARRON, M. T.; WHITESELL, L. Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin. International Journal of Cancer, v.113, n.2, p.179-188, 2005.
  7. BEDIN, M.; GABEN, A. M.; SAUCIER, C.; MESTER, J. Geldanamycin, an inhibitor of the chaperone activity of HSP90, induces MAPK-independent cell cycle arrest. International Journal of Cancer, v.109, n.5, p.643-652, 2004.
  8. BERGMANN, W.; BURKE, D. C. Contributions to the study of marine products. The nucleosides of sponges. Journal of Organic Chemistry, v.20, n.11, p.1501-1507, 1955.
  9. BEUMER, J. H.; RADEMAKER-LAKHAI, J. M.; ROSING, H.; HILLEBRAND, M. J. X.; BOSCH, T. M.; LAZARO, L. L.; SCHELLENS, J. H. M.; BEIJNEN, J. H. Metabolism of trabectedin (ET-743, Yondelisâ„¢) in patients with advanced cancer. Cancer Chemotherapy and Pharmacology, v.59, n.6, p.825-837, 2007.
  10. BRANDON, E. F. A.; SPARIDANS, R. W.; OOIJEN, R. D.; MEIJERMAN, I.; LAZARO, L. L.; MANZANARES, I.; BEIJNEN, J. H.; SCHELLENS, J. H. M. In vitro characterization of the human biotransformation pathways of aplidine, a novel marine anticancer drug. Investigational New Drugs, v.25, n.1, p.9-19, 2007.
  11. CHEN, X.; CHEN, J.; ZHU, J. Synthetic studies on ecteinascidin 743 (Et 743): asymmetric synthesis of a highly oxygenated tetrahydroisoquinoline via a key phenolic Mannich reaction. Synthesis, n.23, p.4081-4086, 2006.
  12. CALABRESI, P.; CHABNER, B. A. Chemotherapy of neoplasic diseases, Em Goodman e Gilman´s: the pharmacological basis of therapeutical, MacGraw-Hill; New York; 2001.
  13. CAUBERT, V.; MASSE, J.; RETAILLEAU, P.; LANGLOIS, N. Stereoselective formal synthesis of the potent proteasome inhibitor: salinosporamide A. Tetrahedron Letters, v.48, n.3, p.381-384, 2007.
  14. CHEN, W.; SHAO, X.; MOELLERING, R.; WENNERSTEN, C.; REGEN, S. L.; Bioconjugate Chemistry, v.17, n.6, p.1582-1591, 2006.
  15. CHLADE-BARTUSIAK, K.; STEMBALSKA-KOZLOWSKA, A.; BERNADY, M.; KUDYBA, M.; SASIADEK, M. Analysis of adaptive response to bleomycin and mitomycin. Mutation Research, Genetic Toxicology and Environmental Mutagenesis, v.513, n.1, p.75-81, 2002.
  16. CHO, J. J.; KIM, Y. T. Sharks: A Potential Source of Antiangiogenic Factors and Tumor Treatments. Marine Biotechnology, v.4, n.6, p.521-525, 2002.
  17. CRAGG, G. M.; NEWMAN, D. J. A Tale of Two Tumor Targets: Topoisomerase I and Tubulin. The Wall and Wani Contribution to Cancer Chemotherapy. Journal of Natural Products, v.67, n.2, p.232-244, 2004.
  18. CUENDET, M.; PEZZUTO, J. M. Antitumor Activity of Bruceantin: An Old Drug with New Promise. Journal of Natural Products, v.67, n.2, p.269-272, 2004.
  19. DE VITA JR., V. T.; HELLMAN, S.; ROSENBERG, S. A. Cancer: Principles of Oncology, LippincottRaven Publishers; Phifadelphia, 1997.
  20. DONIA, M.; HAMANN, M. T. Marine natural products and their potential applications as anti-infective agents. Lancet Infectious Diseases, v.3, n.6, p.338-348, 2003.
  21. ERBA, E.; BASSANO, L.; DI LIBERTI, G. Cell cycle phase perturbations and apoptosis in tumour cells induced by aplidine. British Journal of Cancer, v.86, n.9, p.1510-1517, 2002.
  22. ERBA, E.; BERGAMASCHI, D.; BASSANO, L. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. European Journal of Cancer, v.37, n.1, p.97-105, 2001.
  23. GARCÍA-FERNÁNDEZ, L.F.; LOSADA, A.; ALCALDE, V. Aplidin induces the mitochondrial apoptotic pathway via oxidative stress-mediated JNK and p38 activation and protein kinase C. Oncogene, v.21, n.49, p.7533-7544, 2002.
  24. GARCIA, C. R.; SUPKO, J.G.; MANOLA, J. Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy. Journal of Clinical Oncology, v.22, n.8, p.1480-1490, 2004.
  25. GRACIA, C.; ISIDRO-LLOBET, A.; CRUZ, L. J.; ACOSTA, G. A.; ALVAREZ, M.; CUEVAS, C.; GIRALT, E.; ALBERICIO, F. Convergent Approaches for the Synthesis of the Antitumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups. Journal of Organic Chemistry, v.71, n.19, p.7196-7204, 2006.
  26. GSCHWEND, J.E. Bryostatin 1 induces prolonged activation of extracellular regulated protein kinases in and apoptosis of LNCaP human prostate cancer cells overexpressing protein kinase C. Molecular Pharmacology, v.57, n.6, p.1224-1234, 2000.
  27. HITOTSUYANAGI, Y.; KIM, I. H.; HASUDA, T.; YAMAUCHI, Y.; TAKEYA, K. A structure-activity relationship study of brusatol, an antitumor quassinoid. Tetrahedron, v.62, n.17, p.4262-4271, 2006.
  28. INCA: Instituto Nacional de Câncer. http://www.inca.gov.br/situacao/arquivos/ocorrencia_magnitude_cancerbrasil.pdf; Acessado em 15/04/2007a.
  29. INCA: Instituto Nacional de Câncer. http://www.inca.gov.br/conteudo_view.asp?id=101, Acessado em 15/04/2007b.
  30. JULSING, M. K.; KOULMAN, A.; WOERDENBAG, H. J.; QUAX, W. J.; KAYSER, O. Combinatorial biosynthesis of medicinal plant secondary metabolites. Biomolecular Engineering, v.23, n.6, p.265-279, 2006.
  31. KECK, G. E.; WELCH, D. S.; POUDEL, Y. B. Synthetic studies toward bryostatin 1: preparation of a C1-C16 fragment by pyran annulation. Tetrahedron Letters, v.47, n.47, p.8267-8270, 2006.
  32. KLINDLEN, H. L. Phase II study of flavopiridol in patients with advanced colorectal cancer. Annals of Oncology, v.14, p.1270-1273, 2003.
  33. KOUROUKIS, C. T.; BELCH, A.; CRUMP, M.; EISENHAUER, E.; GASCOYNE, R. D.; MEYER, R.; LOHMANN, R.; LOPEZ, P.; POWERS, J.; TURNER, R.; CONNORS, J. M. Flavopiridol in Untreated or Relapsed Mantle-Cell Lymphoma: Results of a Phase II Study of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology, v.21, n.9, p.1740-1745, 2003.
  34. KUPCHAN, S. M.; BRITTON, R. W.; ZIEGLER, M. F.; SIGEL, C. W. Bruceantin, a new potent anti- leukemic simaroubolide from Brucea antidysenterica. Journal of Organic Chemistry,v.38, n.1, p.178-179, 1973.
  35. LE CESNE, L.; BLAY, J.Y.; JUDSON, I. Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organization for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial. Journal of Clinical Oncology, v.23, n.3, p.576-584, 2005.
  36. LIN, C. M. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Molecular Pharmacology, v.34, n.2, p.200-208, 1988.
  37. MADDEN, T.; TRAN, H. T.; BECK, D.; HUIE, R.; NEWMAN, R. A.; PUSZTAI, L.; WRIGHT, J. J.; ABBRUZZESE, J. L. Novel Marine-derived Anticancer Agents: A Phase I Clinical, Pharmacological, and Pharmacodynamic Study of Dolastatin 10 (NSC 376128) in Patients with Advanced Solid Tumors. Clinical Cancer Research, v.6, n.4, p.1293-1301, 2000.
  38. MANN, J. Natural products in cancer chemotherapy: past, present and future. Nature Reviews Cancer, v.2, n.2, 143-148, 2002.
  39. MINUZZO, M.; MARCHINI, S.; BROGGINI, M.; FAIRCLOTH, G.T.; D’INCALCI, M.; MANTOVANI, R. Interference of transcriptional activation by the antineoplastic drug ecteinascidin-743. Proceedings of the National Academy of Sciences of the United States of America, v.97, n.12, p. 6780-6784, 2000.
  40. NERI, B.; PANTALEO, P.; GIOMMONI, E.; GRIFONI, R.; PAOLETTI, C.; ROTELLA, V.; PANTALONE, D.; TADDEI, A.; MERCATELLI, A.; TONELLI, P. Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study. British Journal of Cancer, v.96, p.1043-1046, 2007.
  41. 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, n.7, p.1022-1037, 2003.
  42. NOVAK, N.; GERDIN, S.; BEROVIC, M. Increased lovastatin formation by Aspergillus terreus using repeated fed-batch process. Biotechnology Letters, v.19, n.10, p.947-948, 1997.
  43. POMMIER, Y. Topoisomerase I inhibitors: camptothecins and beyond. Nature Reviews Cancer, v.6, n.10, p.789-802, 2006.
  44. RADEMAKER-LAKHAI, J.; HORENBLAS, S.; MEINHARDT, W. Phase I Clinical and Pharmacokinetic Study of Kahalalide F in Patients with Advanced Androgen Refractory Prostate Cancer. Clinical Cancer Research, v.11, n.5, p.1854-1862, 2005.
  45. RITU, B.; UMA, S.; NANDANA, S.; MONICA, J.; PAMITA, A.; MANPREET, K.; KUMAR, B. S.; GIRJESH, G. Structure of daunomycin complexed to dTGATCA by two-dimensional nuclear magnetic resonance spectroscopy. European Journal of Medicinal Chemistry, v.41, n.1, p.27-39, 2006.
  46. ROBERT, H.; FELING, G. O.; BUCHANAN, T. J.; MINCER, C. A.; KAUFFMAN, P. R.; FENICAL, W. Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinospora. Angewandte Chemie, International Edition, v.42, n.3, p.355-357, 2003.
  47. ROCHA, A. B.; LOPES, R. M.; SCHWARTSMANN, G. Natural products in anticancer therapy. Current Opinion in Pharmacology, v.1, n.4, p. 364-369,
  48. SCHULTE, T. W.; NECKERS, L. M. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemotherapy and Pharmacology, v.42, n.4, p.273-279, 1998.
  49. SENDEROWICZ, A. M. Flavopiridol: the First Cyclin-Dependent Kinase Inhibitor in Human Clinical Trials. Investigational New Drugs, v.17, n.3,
  50. p.313-320, 1999.
  51. SOLAR, P.; HORVATH, V.; KLEBAN, J.; KOVAL, J.; SOLAROVA, Z.; KOZUBIK, A.; FEODOROCKO, P. Hsp90 inhibitor Geldanamycin increases the sensitivity of resistant ovarian adenocarcinoma cell line A2780cis to cisplatin. Neoplasma, v.54, n.2, p.127-130, 2007.
  52. SPANO, A.; MONACO, G.; BARNI, S.; SCIOLA, L. Expression of cell kinetics and death during monocyte-macrophage differentiation: Effects of actinomycin D and vinblastine treatments. Histochemistry and Cell Biology, v.127, n.1, p.79-94, 2007.
  53. SOUZA, M. V. N. New natural products able to act on the stabilization of microtubules, an important target against cancer. Química Nova, v.27,
  54. n.2, p.308-312, 2004.
  55. STROSBERG, J. R.; KVOLS, L. K. A review of the current clinical trials for gastroenteropancreatic neuroendocrine tumours. Expert Opinion on Investigational Drugs, v.16, n.2, p.219-224, 2007.
  56. SUN, M.; ALKON, D. L. Bryostatin-1: Pharmacology and Therapeutic Potential as a CNS Drug. CNS Drug Reviews, v.12, n.1, p.1-8, 2006.
  57. TEDESCHI, A.; MONTILLO, M.; STROCCHI, E.; CAFRO, A. M.; TRESOLDI, E.; INTROPIDO, L.; NICHELATTI, M.; MARBELLO, L.; BARATE, C.; CAMAGGI, C. M.; MORRA, E. High-dose idarubicin in combination with Ara-C in patients with relapsed or refractory acute lymphoblastic leukemia: a pharmacokinetic and clinical study. Cancer Chemotherapy and Pharmacology, v.59, n.6, p.771-779, 2007.
  58. THUN, M. J.; JEMAL, A.; SIEGEL, R.; WARD, E.; MURRAY, T.; XU, J.; SMIGAL, C. Cancer Statistics. CA-A Cancer Journal for Clinicians, v.56, n.2, p.106-130,2006.
  59. TOKARSKA-SCHLATTNER, M.; ZAUGG, M.; ZUPPINGER, C.; WALLIMANN, T.; SCHLATTNER, U. New insights into doxorubicin-induced cardiotoxicity: The critical role of cellular energetics Journal of Molecular and Cellular Cardiology, v.41, n.3, p.389-405, 2006.
  60. VARTERASIAN, M. L.; MOHAMMAD, R. M.; EILENDER, D. S.; HULBURD, K.; RODRIGUEZ, D. H.; PEMBERTON, P. A.; PLUDA, J. M.; DAN, M. D.; PETTIT, G. R.; CHEN, B. D.; AL-KATIB, A. M. Phase I study of bryostatin 1 in patients with relapsed non-Hodgkin’s lymphoma and chronic lymphocytic leukemia Journal of Clinical Oncology, v.16, n.1, p.56-62, 1998.
  61. VELDHUIZEN, P. J. V.; FAULKNER, J. R.; LARAJR. P. N.; GUMERLOCK, P. H.; GOODWIN, J. W.; DAKHIL, S. R.; GROSS, H. M.; FLANIGAN R. C.;CRAWFORD E. D. Resistance to endocrine therapy in breast cancer. Cancer Chemotherapy and
  62. Pharmacology, v.56, p.39-46, 2005.
  63. VENKAT, R.; MACHERLA, S. M.; RAMA RAO MANAM, R. R.; REED, K. A.; CHAO, T.; NICHOLSON, B.; DEYANAT-YAZDI, G. Structure-Activity Relationship Studies of Salinosporamide A (NPI-0052), a Novel Marine Derived Proteasome Inhibitor. Journal of Medicinal Chemistry, v.48, n.11, p.3684-3687, 2005.
  64. XIE, X.; WATANABE, K.; WOJCICKI, W. A.; WANG, C. C. C.; TANG, Y. Biosynthesis of Lovastatin Analogs with a Broadly Specific Acyltransferase. Chemistry & Biology, v.13, n.11, p.1161-1169, 2006.
  65. WHO: WORLD HEALTH ORGANIZATION. http://www.who.int/mediacentre/factsheets/
  66. fs297/en/index.html; Acessado em 15/04/2007.
  67. ZANGARI, M.; CAVALLO, F.; TRICOT, G. Farnesyltransferase Inhibitors and Rapamycin in the Treatment of Multiple Myeloma. Current Pharmaceutical Biotechnology, v.7, n.6, p.449-453, 2006.

Most read articles by the same author(s)

Author(s)

  • M. V. N. Souza
    Instituto de Tecnologia em Fármacos, Far Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brasil
  • A. C. Pinheiro
    Instituto de Tecnologia em Fármacos, Far Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brasil Instituto de Química, Universidade Federal do Rio de Janeiro Av. Brigadeiro Tromposwski s/n, CT, Bloco A, sala 605 Cidade Universitária, Ilha do Fundão, 21941590 Rio de Janeiro, RJ, Brasil
  • M. L. Ferreira
    Instituto de Tecnologia em Fármacos, Far Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brasil Centro de Estudos Gerais, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho s/n, Centro, 24020-150 Niteroi, RJ, Brasil
  • R. S. B. Gonçalves
    Instituto de Tecnologia em Fármacos, Far Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brasil Instituto de Química, Universidade Federal do Rio de Janeiro Av. Brigadeiro Tromposwski s/n, CT, Bloco A, sala 605 Cidade Universitária, Ilha do Fundão, 21941590 Rio de Janeiro, RJ, Brasil
  • Camilo H. da C. Lima
    Instituto de Tecnologia em Fármacos, Far Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brasil Centro de Estudos Gerais, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho s/n, Centro, 24020-150 Niteroi, RJ, Brasil

Metrics

  • Article viewed 1002 time(s)

How to Cite

1.
Natural Products in Advance Clinical Trials Applied to Cancer. Rev Fitos [Internet]. 2007 Jun. 1 [cited 2024 Nov. 21];3(02):25-42. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/72
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2007 Revista Fitos Eletrônica

Report an error