Marine organisms as a source of new anticancer agents
Abstract
Various active anticancer agents are derived from plants and terrestrial microorganisms. The isolation of C-nucleosides from the Caribbean sponge, Cryptotheca crypta, four decades ago, provided the basis for the synthesis of cytarabine, the first marine-derived anticancer agent to be developed for clinical use. Cytarabine is currently used in the routine treatment of patients with leukaemia and lymphoma. Gemcitabine, one of its fluorinated derivatives, has also been approved for use in patients with pancreatic, breast, bladder, and non-small-cell lung cancer. Over the past decade, several new experimental anticancer agents derived from marine sources have entered preclinical and clinical trials. This field has expanded significantly as a result of improvements in the technology of deep-sea collection, extraction, and large-scale production through aquaculture and synthesis. In this paper, examples of marine-derived experimental agents that are currently undergoing preclinical and early clinical evaluation are briefly discussed. A summary of the available information on the results of phase I and II trials of agents such as aplidine, ecteinascidin-734 (ET-734), dolastatin 10 and bryostatin 1 is also presented.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Depsipeptide (NSC 630176) decreases mRNA expression of the c-MYC oncogene.
“Depsipeptide (NSC 630176), a bicyclic peptide isolated from Chromobacterium violaceum, decreased the mRNA expression of the c-MYC oncogene, causing cell-cycle arrest at G0-G1 and acting as an inhibitor of a histone deacetylase [232].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [232]
Depsipeptide causes cell-cycle arrest at G0-G1.
“Depsipeptide (NSC 630176), a bicyclic peptide isolated from Chromobacterium violaceum, decreased the mRNA expression of the c-MYC oncogene, causing cell-cycle arrest at G0-G1 and acting as an inhibitor of a histone deacetylase [232].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [232]
Depsipeptide acts as an inhibitor of histone deacetylase.
“Depsipeptide (NSC 630176), a bicyclic peptide isolated from Chromobacterium violaceum, decreased the mRNA expression of the c-MYC oncogene, causing cell-cycle arrest at G0-G1 and acting as an inhibitor of a histone deacetylase [232].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [232]
Cites
Natural Products in Drug Discovery and Development
Cragg, G. M. L., Newman, D. J., & Snader, K. M. (1997) · Journal of Natural Products · doi:10.1021/np9604893 · Cited by 1,589 · see citing works
Isolation and structure of bryostatin 1
Pettit, G. R., Herald, C. L., Doubek, D. L., Herald, D. L., Arnold, E., & Clardy, J. (1982) · Journal of the American Chemical Society · doi:10.1021/ja00388a092 · Cited by 653 · see citing works
Ueda, H., Nakajima, H., Hori, Y., Fujita, T., Nishimura, M., Goto, T., & OKUHARA, M. (1994) · The Journal of Antibiotics · doi:10.7164/antibiotics.47.301 · Cited by 493 · see citing works
FR901228, a Potent Antitumor Antibiotic, Is a Novel Histone Deacetylase Inhibitor
Nakajima, H., Kim, Y. B., Terano, H., Yoshida, M., & Horinouchi, S. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4027 · Cited by 484 · see citing works
ter Haar, E., Kowalski, R. J., Hamel, E., Lin, C. M., Longley, R. E., Gunasekera, S. P., Rosenkranz, H. S., & Day, B. W. (1996) · Biochemistry · doi:10.1021/bi9515127 · Cited by 382 · see citing works
Dolastatin 10, a powerful cytostatic peptide derived from a marine animal
Bai, R., Petit, G. R., & Hamel, E. (1990) · Biochemical Pharmacology · doi:10.1016/0006-2952(90)90613-p · Cited by 321 · see citing works
McDaniel, R. N., Ebert‐Khosla, S., Hopwood, D. A., & Khosla, C. (1995) · Nature · doi:10.1038/375549a0 · Cited by 283 · see citing works
Cyclic peptides and depsipeptides from cyanobacteria: A review
Moore, R. E. (1996) · Journal of Industrial Microbiology · doi:10.1007/bf01570074 · Cited by 277 · see citing works
Kowalski, R. J., Giannakakou, P., Gunasekera, S. P., Longley, R. E., Day, B. W., & Hamel, E. (1997) · Molecular Pharmacology · doi:10.1124/mol.52.4.613 · Cited by 262 · see citing works
Ueda, H., Manda, T., Matsumoto, S., Mukumoto, S., Nishigaki, F., Kawamura, I., & Shimomura, K. (1994) · The Journal of Antibiotics · doi:10.7164/antibiotics.47.315 · Cited by 258 · see citing works
Mans, D. R. A., Rocha, A. B., & Schwartsmann, G. (2000) · The Oncologist · doi:10.1634/theoncologist.5-3-185 · Cited by 254 · see citing works
Self-citationCasapullo, A., Bifulco, G., Bruno, I., et al. (2000) · Journal of Natural Products · doi:10.1021/np9903292 · Cited by 219 · see citing works
Ecteinascidin 743: A Minor Groove Alkylator That Bends DNA toward the Major Groove
Zewail‐Foote, M., & Hurley, L. H. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm990241l · Cited by 215 · see citing works
Interference of transcriptional activation by the antineoplastic drug ecteinascidin-743
Minuzzo, M., Marchini, S., Broggini, M., Faircloth, G. T., D’Incalci, M., & Mantovani, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.12.6780 · Cited by 195 · see citing works
Delaloge, S., Yovine, A. J., Taamma, A., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.5.1248 · Cited by 168 · see citing works
The bioprocess–technological potential of the sea
Pomponi, S. A. (1999) · Journal of Biotechnology · doi:10.1016/s0168-1656(99)00053-x · Cited by 164 · see citing works
A phase I study of intravenous bryostatin 1 in patients with advanced cancer
Prendiville, J., Crowther, D., Thatcher, N., Woll, P. J., Fox, B. W., McGown, A. T., Testa, N. G., Stern, P. L., McDermott, R. H., Potter, M., et al. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.352 · Cited by 145 · see citing works
Discovery and Development of Antineoplastic Agents from Natural Sources
Suffness, M., Newman, D. J., & Snader, K. M. (1989) · Bioorganic marine chemistry · doi:10.1007/978-3-642-74560-7_6 · Cited by 145 · see citing works
Ueda, H., Nakajima, H., Hori, Y., et al. (1994) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.58.1579 · Cited by 144 · see citing works
Urdiales, J. L., Morata, P., de Castro, I. N., & Sánchez‐Jiménez, F. (1996) · Cancer Letters · doi:10.1016/0304-3835(96)04151-1 · Cited by 142 · see citing works
Hornung, R. L., Pearson, J. W., Beckwith, M., & Longo, D. L. (1992) · PubMed · Cited by 134 · see citing works
(1997) · PubMed · Cited by 134 · see citing works
Berlinck, R. G. S., Britton, R., Piers, E., et al. (1998) · The Journal of Organic Chemistry · doi:10.1021/jo981607p · Cited by 126 · see citing works
Self-citationJayson, G. C., Crowther, D., Prendiville, J., McGown, A. T., Scheid, C., Stern, P. L., Young, R., Brenchley, P. E., Chang, J., Owens, S. E., et al. (1995) · British Journal of Cancer · doi:10.1038/bjc.1995.356 · Cited by 125 · see citing works
Varterasian, M. L., Mohammad, R. M., Eilender, D., Hulburd, K., Rodriguez, D. H., Pemberton, P. A., Pluda, J. M., Dan, M., Pettit, G. R., Chen, B. D. M., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.1.56 · Cited by 114 · see citing works
The dolastatins, a family of promising antineoplastic agents
Poncet, J. (1999) · Current Pharmaceutical Design · doi:10.2174/1381612805666230109214008 · Cited by 104 · see citing works
Phase I trial of dolastatin-10 (NSC 376128) in patients with advanced solid tumors.
Pitot, H. C., McElroy, E., Reid, J. M., Windebank, A. J., Sloan, J. A., Erlichman, C., Bagniewski, P. G., Walker, D. L., Rubin, J., Goldberg, R. M., et al. (1999) · PubMed · Cited by 101 · see citing works
Polyketides from dinoflagellates: origins, pharmacology and biosynthesis
Rein, K. S., & Borrone, J. W. (1999) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s0305-0491(99)00107-8 · Cited by 100 · see citing works
Clinical trials referral resource.
Cheson, B. D., Abrams, J., McCabe, M. S., et al. (1990) · PubMed · Cited by 94 · see citing works
Madden, T. L., Tran, H. T., Beck, D., et al. (2000) · PubMed · Cited by 90 · see citing works
Discovery and Development of Antineoplastic Agents from Natural Sources
Cragg, G. M. L., & Newman, D. J. (1999) · Cancer Investigation · doi:10.1080/07357909909011730 · Cited by 88 · see citing works
ChemInform Abstract: ISOLATION AND STRUCTURE OF BRYOSTATIN 1
Pettit, G. R., Herald, C. L., Doubek, D. L., et al. (1983) · ChemInform · doi:10.1002/chin.198309065 · Cited by 87 · see citing works
A phase II study of bryostatin 1 in metastatic malignant melanoma
Propper, D., Macaulay, V. M., O'Byrne, K. J., Braybrooke, J. P., Wilner, S., Ganesan, T., Talbot, D., & Harris, A. L. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.680 · Cited by 83 · see citing works
Marine organisms and other novel natural sources of new cancer drugs
Schwartsmann, G. (2000) · Annals of Oncology · doi:10.1093/annonc/11.suppl_3.235 · Cited by 81 · see citing works
Self-citationImmunomodulating properties of a novel series of protein kinase C activators. The bryostatins.
Trenn, G., Pettit, G. R., Takayama, H., Hu‐Li, J., & Sitkovsky, M. V. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.2.433 · Cited by 78 · see citing works
Cytotoxicity and neurocytotoxicity of new marine anticancer agents evaluated using in vitro assays
Geldof, A. A., Mastbergen, S. C., Henrar, R. E. C., et al. (1999) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050983 · Cited by 69 · see citing works
Phase II study of dolastatin-10 in patients with advanced non-small-cell lung cancer
Krug, L. M., Miller, V. A., Kalemkerian, G. P., et al. (2000) · Annals of Oncology · doi:10.1023/a:1008349209956 · Cited by 64 · see citing works
Phase-trafficking reagents and phase-switching strategies for parallel synthesis
Flynn, D. L. (1999) · Medicinal Research Reviews · doi:10.1002/(sici)1098-1128(199909)19:5 · Cited by 61 · see citing works
Christian, M. C., Pluda, J. M., Ho, P. T. C., et al. (1997) · PubMed · Cited by 57 · see citing works
Garcı́a-Rocha, M., García-Gravalos, M., & Ávila, J. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.176 · Cited by 52 · see citing works
Shin, D. M., Holoye, P. Y., Murphy, W. K., et al. (1991) · Cancer Chemotherapy and Pharmacology · doi:10.1007/bf00687325 · Cited by 50 · see citing works
Kahalalide K: A New Cyclic Depsipeptide from the Hawaiian Green Alga Bryopsis Species
Kan, Y., Fujita, T., Sakamoto, B., et al. (1999) · Journal of Natural Products · doi:10.1021/np990053y · Cited by 37 · see citing works
Makaluvamines vary in ability to induce dosedependent DNA cleavage via topoisomerase II interaction
Matsumoto, S. S., Haughey, H. M., Schmehl, D. M., et al. (1999) · Anti-Cancer Drugs · doi:10.1097/00001813-199901000-00006 · Cited by 33 · see citing works
Pathak, S., Multani, A. S., Ozen, M., Richardson, M. A., & Newman, R. A. (1998) · Oncology Reports · doi:10.3892/or.5.2.373 · Cited by 32 · see citing works
Summary of the Workshop on Drug Development, Biological Diversity, and Economic Growth
Schweitzer, J., Handley, F. G., Edwards, J. D., et al. (1991) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/83.18.1294 · Cited by 32 · see citing works
Antitumor activity of cryptophycins: effect of infusion time and combination studies
Menon, K., Álvarez, E., Forler, P., et al. (2000) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800000135 · Cited by 32 · see citing works
A phase II trial of didemnin B in myeloma
Weiss, R. B., Peterson, B. L., Allen, S. L., et al. (1994) · Investigational New Drugs · doi:10.1007/bf00873234 · Cited by 27 · see citing works
Bioactive Sesquiterpenes from A Taiwanese Marine Sponge Parahigginsia sp.
Chen, C., Shen, Y., Chen, Y., et al. (1999) · Journal of Natural Products · doi:10.1021/np980491p · Cited by 24 · see citing works
Anticancer drug screening and discovery in the 1990s: a European perspective
Schwartsmann, G., & Workman, P. (1993) · European Journal of Cancer · doi:10.1016/0959-8049(93)90567-y · Cited by 23 · see citing works
Self-citation(2000) · PubMed · Cited by 21 · see citing works
Anti-tumor Marine Natural Products.
Kitagawa, I., & Kobayashi, M. (1991) · Journal of Synthetic Organic Chemistry Japan · doi:10.5059/yukigoseikyokaishi.49.1053 · Cited by 11 · see citing works
Clinical trials referral resource. Clinical trials of dolastatin-10.
Jj, W., Blatner, G. L., & Bd, C. (1999) · PubMed · Cited by 10 · see citing works
Phase II study of ET-743 in advanced soft-tissue sarcoma (ASTS) in adult: A STBSG-EORTC trial
Cesne, A. L., Judson, I. R., Radford, J. A., et al. (2000) · Research Explorer (The University of Manchester) · Cited by 9 · see citing works
ChemInform Abstract: Antitumor Marine Natural Products
Kitagawa, I., & Kobayashi, M. (1992) · ChemInform · doi:10.1002/chin.199218336 · Cited by 4 · see citing works
Rinehart (2000) · doi:10.1002/(sici)1098-1128(200001)20:1
Flagged first, then by citations
Cited by
Sorted by citations
Marine Natural Products: A Source of Novel Anticancer Drugs
Khalifa, S. A. M., Elias, N., Farag, M. A., Chen, L., Saeed, A., Hegazy, M.-E. F., Moustafa, M. S., Abd El-Wahed, A., Al-Mousawi, S. M., Musharraf, S. G., et al. (2019) · Marine Drugs · doi:10.3390/md17090491 · Cited by 555 · see citing works
Immense essence of excellence: Marine microbial bioactive compounds
Bhatnagar, I., & Kim, S.-K. (2010) · Marine Drugs · doi:10.3390/md8102673 · Cited by 384 · see citing works
Evaluation of microalgae and cyanobacteria as potential sources of antimicrobial compounds
Alsenani, F., Tupally, K. R., Chua, E. T., Eltanahy, E., Alsufyani, H., Parekh, H. S., & Schenk, P. M. (2020) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2020.11.010 · Cited by 149 · see citing works
- Authors
- Schwartsmann, G., da Rocha, A. B., Berlinck, R. G., & Jimeno, J.
- Affiliations
- Universidade Luterana do Brasil (BR)
- Instituto de Química de São Carlos (BR)
- Corresponding author
- Schwartsmann, Gilberto
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 2
- Issue
- 4
- Pages
- 221-225
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2111604285
- Cited by
- 261
- References
- 55
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 17 · 2021: 13 · 2020: 19 · 2019: 12 · 2018: 15 · 2017: 9 · 2016: 14 · 2015: 21 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Synthesis and Biological Activity
- Keywords
- marine-derived anticancer agents, marine sponges, C-nucleosides, cytarabine, gemcitabine, dolastatin 10, bryostatin 1, marine natural products, leukemia, lymphoma, pancreatic cancer, breast cancer, non-small cell lung cancer
- MeSH terms
- Animals, Antineoplastic Agents, Clinical Trials as Topic, Drug Evaluation, Preclinical, Forecasting, Humans, Lactones, Neoplasms, Urochordata, Macrolides, Bryostatins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
