Table 1: Anticancer drugs from marine animals

Drug name	Source	Mechanism of action/Target molecule or pathway	Compound nature	Can be used against
Halichondrin B	Halichondria okadai⁽⁵⁾	Tubulin targeted mitotic inhibitor⁽⁴⁾	Polyether macrolide⁽⁵⁾	Hematological cancer⁽⁶⁾
Trabectedin (Ecteinascidin 743)	Caribbean tunicate Ecteinascidia turbinata⁽⁷⁾	Minor groove of DNA⁽⁷⁾	Alkaloid⁽⁷⁾	Soft tissue sarcoma⁽⁸⁾⁽⁹⁾, Liposarcoma and Leiomyosarcoma⁽⁹⁾
Bryostatin	Bugula neritina^(11)(12)	Downregulation of PKC⁽¹⁰⁾	Macrocyclic lactone⁽¹⁰⁾	Melanoma, Lymphoma, Reticulum cell sarcoma, Ovarian carcinoma, Leukemia, Lung cancer⁽¹²⁾
Discodermolide	Discodermia dissoluta (Carribean deep water marine sponge) ⁽¹³⁾	Microtubule stabilizer⁽¹⁴⁾	Polyhydroxylated lactone⁽¹³⁾	Breast carcinoma⁽¹⁴⁾
Dolastatin	Dolabella auricularia⁽¹⁶⁾	Microtubule inhibitor⁽¹⁵⁾	Cytotoxic peptide⁽¹⁵⁾	Prostate adenocarcinoma⁽¹⁵⁾
Kahalalide F	Elysia rufescens⁽¹⁸⁾	Cell death via oncosis⁽¹⁸⁾	Cyclic depsipeptide⁽¹⁷⁾	Human prostate cancer, Breast cancer ⁽¹⁸⁾
Squalamine	Dogfish shark Squalus acanthias^(19)(20)	Anti-angiogenic⁽¹⁹⁾	Aminosteroid⁽²⁰⁾	Ovarian cancer⁽¹⁹⁾
Dehydrodidemnin B (Plitidepsin)(Aplidin)⁽²³⁾	Mediterranean tunicate Aplidium albicans^(21)(22)	Activation of Rac1 GTPase and the inhibition of protein phosphatises⁽²²⁾	Depsipeptide ^(21)(23)	Human colon cancer⁽²¹⁾
Vitilevuamide	(i)Didemnum cuculiferum (ii)Polysyncraton lithostrotum,^(24)(25)	Tubulin inhibition^(24)(25)	Bicyclic depsipeptide⁽²⁴⁾	Human cancer cell lines, Mouse lymphocytic leukemia⁽²⁵⁾
Eleutherobin	Marine coral Eleutherobia sp.(Corals in Australia)⁽²⁶⁾	Microtubulin bundling leading to mitotic arrest⁽²⁶⁾	Glycosylated terpene⁽²⁸⁾	Clinical study going on⁽²⁷⁾
Sarcodictyin	Bellonella albiflora⁽²⁹⁾	Microtubule stabilization/Tubulin polymerization⁽³⁰⁾	Diterpenoid⁽²⁹⁾	Cervical cancer cells/HeLa cells⁽²⁹⁾
Peloruside	New Zealand sponge Mycale hentscheli⁽³²⁾	Microtubule stabilizer ⁽³²⁾	Macrocyclic secondary metabolite⁽³²⁾	Ovarian carcinoma⁽³¹⁾
Ascididemnin	(i) Didemnum sp.⁽³³⁾ (ii) Cystodytes dellechiajei⁽³⁴⁾	Inhibits topoisomerase activity ⁽³³⁾	Pentacyclic aromatic alkaloid ⁽³³⁾	Leukemia⁽³⁴⁾
Lamellarin D	Oceanic sea snail Lamellaria sp.⁽³⁵⁾	Mitochondrial topoisomerase inhibition⁽³⁶⁾	Hexacyclicpyrrole alkaloid ⁽³⁶⁾	Human prostate cancer and leukemia⁽³⁷⁾
Dictyodendrin	(i) Dictyodendrilla verongifermis⁽³⁹⁾ (ii) Ianthella sp.⁽⁴⁰⁾	Inhibits telomerase activity⁽³⁸⁾	Alkaloid ⁽³⁸⁾	Colon cancer cell lines⁽⁴⁰⁾
ES-285(Spisulosine)	Mactromeris polynima(Marine mollusc) Also known as Spisula polynyma^{(41) (42)}	Activates caspase 3 and 12 which further induces apoptosis⁽⁴¹⁾	Sphingolipid derivative ⁽⁴¹⁾	Lymphomas, Leukemias, Prostate cancer, Renal cancer, Hepatocarcinoma, Colon cancer and Melanoma ⁽⁴²⁾
Fascaplycin	Fascaplysinopsis sp.⁽⁴³⁾.	Anti-angiogenic, specific inhibition of cyclin-dependent kinase-4, p56 tyrosine kinase inhibition ⁽⁴³⁾	Indole alkaloid ⁽⁴³⁾	Small cell lung cancer⁽⁴⁴⁾
Aaptamine	Aaptos aaptos⁽⁴⁵⁾	DNA intercalating activity ⁽⁴⁶⁾	Bioactive benzo[de][1,6]-naphthyridine⁽⁴⁶⁾	Hepatocellular carcinoma ⁽⁴⁷⁾
Agosterol A	Spongia sp.⁽⁴⁸⁾	Directly inhibited drug efflux through PgP and MRP1 ⁽⁴⁹⁾	Polyhydroxylated sterol acetate ⁽⁴⁸⁾	Reverses multidrug resistance in human carcinoma cells ⁽⁴⁸⁾
Aplyronine A	Sea hare Aplysia kurodai⁽⁵⁰⁾	Inhibits polymerization of actin F filaments ⁽⁵⁰⁾	Macrolide ⁽⁵⁰⁾	Cervical cancer cells/HeLa cells⁽⁵¹⁾
Bistramide A	(i) Trididemnum cyclops (ii) Lissoclinum bistratum⁽⁵²⁾	Severing of actin filaments and covalent sequestration of monomeric actin in the cell ⁽⁵³⁾	Lipopeptide⁽⁵²⁾	A549 cells /adenocarcinomic human alveolar basal epithelial cells ⁽⁵³⁾
Bromovulone III	Soft coral Clavularia viridis⁽⁵⁴⁾	Induced mitochondria related activation of caspase-9 and 3⁽⁵⁴⁾	Prostanoid⁽⁵⁴⁾	Prostate cancer PC-3 and acute promyelocytic leukemia HL-60 cells, Hepatocellular carcinoma⁽⁵⁴⁾
Cortistatin A	Marine sponge Corticium simplex ⁽⁵⁵⁾	Anti-angiogenic⁽⁵⁵⁾	Steroidal alkaloid⁽⁵⁵⁾	Human umbilical vein endothelial cells (HUVECs)⁽⁵⁵⁾
Onnamide	Theonella sp. (sponge) ⁽⁵⁶⁾	Inhibition of protein synthesis ⁽⁵⁶⁾	Heterocyclic compound ⁽⁵⁶⁾	Murine and human tumor cells ⁽⁵⁶⁾
Mycaperoxide H	Thai marine sponge Mycale sp.⁽⁵⁷⁾		Norsesterterpene Peroxide⁽⁵⁷⁾	HeLa cells⁽⁵⁷⁾
Cytarabine	Cryptotheca crypta⁽⁵⁸⁾	Inhibits DNA replication⁽⁵⁹⁾	Cytotoxic nucleoside analogue⁽⁶⁰⁾	Leukemia and lymphoma⁽⁵⁸⁾
Laulimalide	Hyattella sp.and Fasciospongia rimosa⁽⁶²⁾	Promotes abnormal tubulin polymerization and apoptosis⁽⁶¹⁾	Macrolide⁽⁶¹⁾	KB,P388,A549,HT29,MEL28 cell lines⁽⁶²⁾

Table 2: Anticancer drugs from marine microbes

Drug name	Source	Mechanism of action/Target area or molecule	Compound nature	Can be used against
Didemnin b	(i) Trididemnum solidum (ii) Tistrella mobilis (iii) Tistrella bauzanensis⁽⁶³⁾	Induces rapid and wholesale apoptosis through dual inhibition of PPT1 and EEF1A1 ⁽⁶⁵⁾	Cyclic depsipeptide⁽⁶³⁾	B16 melanoma, M5076 sarcoma and P388 leukemia⁽⁶⁴⁾
Symplocamide	Marine cyanobacterium Symploca sp.^{(66) (68)}	Protease inhibitor⁽⁶⁶⁾	Cyclic depsipeptide^{(67) (68)}	H460 lung cancer and neuro-2A neuroblastoma cell lines ⁽⁶⁸⁾
Curacin A	Lyngbya majuscula⁽⁶⁹⁾	Inhibits microtubule assembly⁽⁶⁹⁾	Lipid⁽⁶⁹⁾	Colon cancer, Renal cancer, Breast cancer⁽⁶⁹⁾
Salinosporamide A (NPI-0052)	Salinospora tropica^{(70) (71)}	Inhibits ubiquitin-proteasome^(70)(71)	Gamma-Lactam and Beta-Lactone derivative^{(70) (71)}	Multiple myeloma, solid tumors or lymphoma⁽⁷¹⁾
Thiocoraline	Marine actinomycete Micromonospora marina^{(72) (73)}	Inhibition of DNA replication by inhibiting polymerase α⁽⁷²⁾	Cyclic thiodepsipeptide⁽⁷³⁾	Human non-small cell lung cancer, Breast cancer, Colon cancer, Renal cancer, Melanoma cancer⁽⁷²⁾
DMMC(ethoxymajusculamide C)	Lyngbya majuscula⁽⁷⁴⁾	Stimulates microfilament hyperpolymerization⁽⁷⁴⁾	Depsipeptide⁽⁷⁴⁾	Human colon cancer, Human lung cancer, human breast cancer and human leukemia⁽⁷⁴⁾
Microviridins	Freshwater cyanobacterium Microcystis sp.⁽⁷⁵⁾	Inhibits serine-type proteases⁽⁷⁵⁾	Cyclic depsipeptide⁽⁷⁵⁾	-
Borophycin	Nostoc linckia⁽⁷⁶⁾	-	Boron incorporated compound⁽⁷⁶⁾	Human epidermoid carcinoma(LoVo) and human colorectal adenocarcinoma⁽⁷⁶⁾
Apratoxin A	Marine cyanobacterium Lyngbya majuscula^(78)(79)	Induces G1 phase cell cycle arrest and apoptosis^{(77) (79)}	Cyclodepsipeptide^{(78) (79)}	Early stage adenocarcinoma⁽⁷⁹⁾
Cryptophycin 1	Nostoc sp.⁽⁸¹⁾	Suppressor of microtubule dynamics^(80)(83)	Depsipeptide family⁽⁸²⁾	HeLa cell lines⁽⁸³⁾ Human prostate cancer cells ⁽⁸⁴⁾
Largazole	Symploca sp.⁽⁸⁵⁾	Inhibits class I histone deacetylases(HDACs)⁽⁸⁵⁾	Cyclic depsipeptide⁽⁸⁵⁾	Human malignant melanoma, human epithelial carcinoma, breast cancer, lung cancer, prostate cancer and leukemia⁽⁸⁵⁾
Coibamide	Marine cyanobacterium Leptolyngbya from Coiba National Park, Panama^(86)(87)	Inhibits extracellular VEGFA and arrests G1 cell cycle⁽⁸⁶⁾	Cytotoxic lariat depsipeptide^(86)(87)	Glioblastoma and breast cancer⁽⁸⁶⁾
Scytonemin	Lyngbya aestuarii⁽⁸⁹⁾Calothrix sp.⁽⁹⁰⁾	Inhibits the activity of Plk1(polo-like kinase 1)⁽⁸⁸⁾	Tricyclic ketone which undergoes oxidative transformations and dimerization to form the compound⁽⁸⁹⁾	Multiple myeloma⁽⁸⁸⁾
Lyngbyabellin A	Marine cyanobacterium Lyngbya majuscula⁽⁹¹⁾	Microfilament disruptor⁽⁹²⁾	Cyclic Depsipeptide⁽⁹¹⁾	Human lung cancer, Neuroblastoma⁽⁹³⁾
Daunorubicin	Streptomyces peucetius⁽⁹⁴⁾	Intercalation with the DNA leading to interference in RNA synthesis⁽⁹⁴⁾	Pigmented aglycone in glycoside linkage with an amino sugar ⁽⁹⁴⁾	Leukemia, Rhabdomyosarcoma, Neuroblastoma ⁽⁹⁴⁾

Table 3: Anticancer drugs extracted from marine plants

Drug name	Source	Mechanism of action/Target area or molecule	Compound nature	Can be used against
Phloroglucinol	Ecklonia cava⁽⁹⁵⁾	Induces apoptosis⁽⁹⁵⁾	Polyphenolic compound⁽⁹⁵⁾	Colorectal carcinoma, breast cancer⁽⁹⁵⁾
Stypoldione	Stipopodium zonale⁽⁹⁶⁾	Gets added to the thiold containing tubulin protein⁽⁹⁶⁾	Compound has o-quinone⁽⁹⁶⁾	Lymphocytic leukemia⁽⁹⁶⁾
Condriamide A	Chondria sp.⁽⁹⁷⁾	Cytotoxic to cancer cells⁽⁹⁷⁾	-	Human nasopharyngeal and colorectal cancer⁽⁹⁷⁾
Caulerpenyne	Caulerpa taxifolia⁽⁹⁸⁾	Inhibits microtubule polymerization⁽⁹⁸⁾	Secondary metabolite⁽⁹⁸⁾	Neuroblastoma⁽⁹⁸⁾
Fucoxanthin	Phaeodactylum tricornutum⁽¹⁰⁰⁾	Influences caspases, Bcl-2 proteins, MAPK, P13K/Akt, JAK/STAT, AP-1, GADD45⁽⁹⁹⁾	Carotenoid^(99)(100)	Liver cancer, Breast cancer, Prostate cancer, Colon cancer and lung cancer, Osteosarcoma etc.,⁽⁹⁹⁾
Halomon	Portieria hornemannii⁽¹⁰¹⁾	Inhibits DNA methyltransferase-1⁽¹⁰¹⁾	Polyhalogenated monoterpene⁽¹⁰¹⁾	NCI-60 human tumor cell line⁽¹⁰¹⁾

DISCUSSION:

Porifera, Chordata, Cnidaria and Mollusca are the major phyla in the animal kingdom from where the drugs are extracted. Among all these phyla, Porifera tops the list. Sponges, which come under phylum Porifera have been exploited to the maximum when compared to other animals. A variety of sponges like Discodermia dissoluta, Halichondria okadai, Mycale hentscheli, Dictyodendrilla verongifermis, Corticium simplex, Theonella sp. Cryptotheca crypta, Aaptos aaptos act as potential sources till date. Second most common phylum used for anticancer drug extraction is Phylum Chordata. Tunicates like Aplidium, Didemnum, Polysyncraton, Lissoclinum, Trididemnum are potential sources for anticancer drugs. Next comes the phylum mollusc. Elysia rufescens, Dolabella sp. Spisula polynyma, Oceanic sea snails, Aplysia kurodai and all sea hares are the common molluscs that possess compounds with anticancer activity. Corals placed under Phylum Cnidaria also contribute significantly to the medical field. Bellonella albiflora, Sarcodictyon roseum, Eleutherobia sp. Clavularia viridis are corals that are being used in pharmaceutical industry. Bryozoa is a phylum that consists of aquatic invertebrates. Bugula neritina is one such organism that produces a compound which can down regulate PKC. Table 1 lists all the major drugs that are extracted from the above mentioned animals. Their mechanism of action includes microtubule destabilisation, cell death via oncosis, PgP inhibition, topoisomerase inhibition, Caspase 3 and 12 activation, actin F inhibition, anti-angiogenic activity. With these mechanisms they are able to effectively destroy the rapidly growing cancer cells. Table 2 lists the anticancer drugs extracted from marine microbes. Cyanobacteria are also known as blue green alga. They are a class of photosynthetic bacteria. Lyngbya sp. Nostoc sp. Symploca sp. and Stigonema sp. are cyanobacteria that produce metabolites with antitumor activity. Salinospora sp. and Micromonospora sp. come under the family of micromonosporaceae and order of actinomycetales. Salinosporamide A and thiocoraline are the compounds produced by these microbes respectively. Table 3 lists the anticancer drugs obtained from marine plants. These marine plants mainly include macroalga like sea weeds. Brown alga like Ecklonia sp. Stipopodium sp. Red alga like Chondria sp. Portieria sp. and green alga like Caulerpa sp. are the main plant sources used so far. Phaeodactylum is a diatom from which fucoxanthin is being isolated. Fucoxanthin influences MAPK pathway thereby inhibiting cell proliferation.

CONCLUSION:

Cancer is one among the deadliest disease known to mankind. It is the major cause of death in both developed and under-developed countries. Scientists are of the view that this scenario is likely to worsen as time progresses. So there is always a great demand for a potential anticancer drug. Marine environment still has lots of flora and fauna undiscovered. Many of the marine anticancer drugs still need to be explored. If this is done it can be the solution for a variety of problems. Extensive research should be done in this area. These compounds will be of great use to mankind in treating several disorders in the future. Research that is put into the marine biome will never become a waste. It will always provide us with lots of valuable compounds. This will open doors to the discovery of many drugs that will benefit humans. Many life saving drugs can be discovered. By doing this we can combat various health problems, especially cancer, which will be on the rise in the near future.

ACKNOWLEDGEMENTS:

We acknowledge VIT University, Vellore, Tamil Nadu for support. We are grateful to Ms.Padmapriya Ravi for extending her valuable suggestions in writing the manuscript.

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