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Marine Drugs
Marine drugs are pharmaceutical compounds that have been isolated or derived from marine organisms. Marine pharmacology is a novel field, and there is no set method of extracting and characterizing desired compounds. Some promising substances are the well-characterized results of substantial chemical processing with organic chemistry techniques, while others are simply crude extracts that lack proper characterization.
Researchers screen compounds for antiangiogenic, apoptotic, and cytotoxic activity, which are essential for any drug used to treat cancer.
Natural products have overwhelmingly shown the most promise as anticancer treatments [1] . Marine organisms have been an important source for potential cancer drugs, beginning with trabectedin, the first marine anticancer drug to be approved [2] .
Marine Sources[edit]
Researchers are actively investigating organisms from different taxonomic backgrounds in search of substances with anticancer activity. Phyla in the animal kingdom that have been particularly prolific include porifera, mollusca, and echinodermata. The plant and fungi kingdoms have also yielded promising compounds.
Animalia[edit]
Porifera[edit]
The porifera phylum includes sponges, which have yielded a wealth of interesting compounds, including smenospongine, yaku’amide A, and spongistatin 1.
Smenospongine, a sesquiterpene aminoquinone from Dactylospongia elegans, exhibited antiangiogenic activitiy against solid tumors. Smenospongine inhibits growth of blood vessels necessary for tumors to take in nutrients. Smenospongine also displays apoptotic effects against leukemia cells, which do not need HUVECs to survive [3] .
Yaku’amide A was isolated from Ceratopsion sp. When tested against murine leukemia cells, it exhibits cytotoxic effects. Yaku’amide A is potentially toxic to cells through a different mechanism than many other drugs currently on the market [4] .
Spongistatin 1 has apoptotic and cytotoxic effects against pancreatic tumor cells in vitro. Spongistatin 1 has been studied in vivo against human pancreatic cancer in mice. Spongistatin reduces tumor growth and inhibits the spread of the cancer. It phosphorylates (and thus deactivates) Bcl-2, a protein that protects cancer cells from apoptosis and aids in cell migration [5] .
Mollusca[edit]
The mollusca phylum includes oysters and sea snails. Hydrolysate extracts of oyster proteins stimulate the immune system during the process of recovering from cancer. Immunostimulating effects have also been demonstrated in mice. These extracts increase the activity of natural killer cells and macrophages and the production of lymphocytes [6] .
Lamellin-D, from the sea snail Lamellaria sp., induces apoptosis by inhibiting topoisomerase I, an enzyme which facilitates the DNA replication of cancer cells. Lamellin-D interferes with the ability of the cancer cell to produce the ATP that is needed for cellular functions. Lamellin-D inhibits cyclin-dependent kinases, molecules involved in the overactive cell cycle of cancer cells. Apoptosis normally only occurs in dying cells, but lamellin-D affects cells such that apoptosis is induced even in thriving cancer cells [7] .
Echinodermata[edit]
The echinodermata phylum includes sea cucumbers and tunicates. Echinoside A, from the sea cucumber Holothuria nobilis, inhibits topoisomerase II alpha, which in turn blocks cell growth. Topoisomerase II inhibitors are powerful anticancer drugs, but they are highly toxic because they interfere with ATP-dependent reactions and may induce tumor multidrug resistance. Echinoside A, however, inhibits topoisomerase II alpha in a way that does not lead to such toxic effects <nowiki>Insert non-formatted text here</nowiki> [8] .
An extract from the tunicate Polyclinum indicum induces apoptosis in cervical cancer cells and inhibits proliferation. This compound is thought to be less toxic than other chemotherapeutics[9] . Ascididemin, from a Didemnum sp. tunicate, inhibits topoisomerase II and prevents the growth of human and murine leukemia cells. It induces apoptosis, interferes in the cancer cell’s ability to produce ATP, and generates DNA-damaging reactive oxidative species [10] .
Plantae[edit]
Spirulina maxima has cytotoxic effects, and can select for human digestive tract cancers (stomach and liver) when extracted with ultrasonication. C phycocianin, from Spirulina platensis, decreases the production of multidrug resistance-1, which makes some types of human hepatocarcinoma resistant to chemotherapeutics. It also makes tumors more sensitive to treatment [11] .
Crude extract from Spyridia filamentosa reduces cell viability of human prostate carcinoma by up to 90%, and of human breast adenocarcinoma by 80%. Cystoseira medinerranea reduces viability by up to 55% [12].
Fungi[edit]
SZ-685C, an anthracycline analogue found in a species of endophytic fungi, induces apoptosis in human breast cancer, prostate cancer, glioma, and hepatoma cancers. No signs of discomfort or weight loss were observed in mice. Anthracyclines are generally powerful, yet toxic, treatments, so SZ-685C is a promising compound [13].
Mycoepoxydiene, isolated from an unidentified marine fungus, induces apoptosis and arrests cell growth. Notably, these powerful effects do not harm other healthy cells, which is an improvement over many current anticancer drugs [14] .
Aspergilone A, derived from Aspergillus sp., is cytotoxic against several human cancer cell lines, including promylocytic leukemia, breast adenocarcinoma, and lung carcinoma [15] .
Obstacles[edit]
Researchers have determined anticancer potential for many marine-derived compounds, yet functional mechanisms are not commonly elucidated. A thorough understanding of the mechanism of action is essential to proceed with in vivo trials, especially in humans. In vivo studies are rare in the literature because many compounds have not been sufficiently characterized.
Large scale manufacturing of marine drugs requires massive harvests of the organism. This poses practical problems regarding financial expenses, growing spaces, and storage locations. More importantly, the environmental impacts would be devastating to an organism and its ecosystem if the organism could not be sustainably harvested. Fungi would be useful in this respect, because only small amounts of harvested specimen are necessary to grow large cultures.
References[edit]
- ^ Harvey, A. (2010). "High-throughput screening of natural products for cancer therapy". Planta Medica. 76 (11): 1080–1086. doi:10.1055/s-0030-1250162. PMID 20635309.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Gordaliza, M (2010). "Cytotoxic terpene quinones from marine sponges". Marine Drugs. 8 (12): 2849–2870. doi:10.3390/md8122849. PMC 3039459. PMID 21339953.
- ^ Kong, D. (2008). "Antiproliferative and antiangiogenic activities of smenospongine, a marine sponge sesquiterpene animoquinone". Marine Drugs. 9 (2): 154–161. doi:10.3390/md9020154. PMC 3093250. PMID 21566792.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Ueoka, R. (2010). "Yaku'amides A and B, cytotoxic linear peptides rich in dehydroamino acids from the marine sponge Ceratopsion sp". Journal of the American Chemical Society. 132 (50): 17692–17694. doi:10.1021/ja109275z. PMID 21121605.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Rothmeier, A. (2010). "The marine compound spongistatin 1 targets pancreatic tumor progression and metastasis". International Journal of Cancer. 127 (5): 1096–1105. doi:10.1002/ijc.25241. PMID 20143389.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Wang, Y (2010). "Oyster (Crassostrea gigas) hydrolysates produced on a plant scale have antitumor activity and immunostimulating effects in BALB/c mice". Marine Drugs. 8 (2): 255–268. doi:10.3390/md8020255. PMC 2852837. PMID 20390104.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Bayet-Robert, M (2010). "Biochemical disorders induced by cytotoxic marine natural products in breast cancer cells as revealed by proton NMR spectroscopy-based metabolomics". Biochemical Pharmacology. 80 (8): 1170–1179. doi:10.1016/j.bcp.2010.07.007. PMID 20637732.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Li, M (2010). "Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase II alpha by unique interference with is DNA binding and catalytic cycle". Annals of Oncology. 21 (3): 597–607. doi:10.1093/annonc/mdp335. PMID 19773249.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Rajesh, R (2010). "Anticancer activity of the Ascinian Polyclinum Indicum aganst cervical cancer cells (HeLa) mediated through apoptosis induction". Medicinal Chemistry. 6 (6): 396–405. doi:10.2174/157340610793564009. PMID 21054277.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Bayet-Robert, M (2010). "Biochemical disorders induced by cytotoxic marine natural products in breast cancer cells as revealed by proton NMR spectroscopy-based metabolomics". Biochemical Pharmacology. 80 (8): 1170–1179. doi:10.1016/j.bcp.2010.07.007. PMID 20637732.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Nishanth, R (2010). "C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line". European Journal of Pharmacology. 649 (1–3): 74–83. doi:10.1016/j.ejphar.2010.09.011. PMID 20858479.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Taskin, E (2010). "Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the eastern Mediterranean sea". African Journal of Biotechnology. 9 (27): 4272–4277.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Xie, G (2010). "SZ-685C, a marine anthraquinone, is a potent inducer of apoptosis with anticancer activity by suppression of the Akt/FOXO pathway". The British Journal of Pharmacology. 159 (3): 689–697. doi:10.1111/j.1476-5381.2009.00577.x. PMC 2828032. PMID 20128807.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Wang, J (2010). "Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells". Bioorganic & Medicinal Chemistry Letters. 20 (23): 7054–7058. doi:10.1016/j.bmcl.2010.09.105. PMID 20970330.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Shao, C (2011). "Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton from the gorgonian-derived fungus Aspergillus sp". Bioorganic & Medicinal Chemistry Letters. 21 (2): 690–693. doi:10.1016/j.bmcl.2010.12.005. PMID 21194945.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)