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Mode of Action of Ascidians: a New Gateway in the Era of Anticancerous Activity

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Mode of Action of Ascidians: a New Gateway in the Era of Anticancerous Activity Mukt Shabd Journal ISSN NO : 2347-3150 Mode of action of ascidians: A new gateway in the era of anticancerous activity Jain Seema Sachin Department of Biotechnology, Shree Ramkrishna Institute of Computer Education & Applied Sciences, Veer Narmad South Gujarat University, Surat, Gujarat, India Marjadi Darshan Sunil Department of Biotechnology, Shree Ramkrishna Institute of Computer Education & Applied Sciences, Veer Narmad South Gujarat University Surat, Gujarat, India ABSTRACT Ascidians (tunicates) are invertebrate chordates, and prolific producers of a wide variety of biologically active secondary metabolites from cyclic peptides to aromatic alkaloids. Several of these compounds have properties which make them candidates for potential new drugs to treat diseases such as cancer. Among the first six marine derived compounds that have reached clinical trials as antitumor agents, three are derived from ascidians, evidence of the high potential of these organisms as a new source of antitumor compounds. Cancer is a complex disease involving cell transformation, dysregulation of apop.tosis, proliferation, invasion, angiogenesis and metastasis. Indeed, ascidian-derived natural products have yielded promising drug leads, among which ecteinascidin 743 (Yondelis®) and dehydrodidemnin B (Aplidin®) are in clinical usage for the treatment of specific cancers. Treatment for cancer does not have potent medicine as the currently available drugs are causing side effects in some instances. New drugs with milder side effects are needed to replace and improve existing medicine. In this context, the natural products derived from marine organisms have gained significance. The current study aims at evaluating anticancer activity of ascidians against various cell lines and mode of action of compounds obtained from ascidians. Keywords: Ascidians, Secondary metabolites, Bacterial symbiosis, anticancer activity, Mechanism of action, Marine Natural Product 1. INTRODUCTION Ascidians (urochordates, tunicates), commonly known as sea-squirts, belong to the Phylum, Chordata; sub-phylum; Tunicata; class, Ascidiacea. Ascidians are exclusively marine, abundant in harbors, and can be found all over the world from near the surface to great depths. The three orders within the class Ascidiacea, based on the structure of the adult branchial sac, are Aplousobranchia (almost exclusively colonial), Phlebobranchia, and Stolidobranchia (in both solitary and colonial forms. Ascidians, along with sponges and bryozoans, produce a rich variety of secondary metabolites presumably to avoid predation and as an anti-fouling mechanism. Anti-cancer drugs are the main area of interest in the screening of Marine Natural Products from ascidians (64%), followed by anti-malarial (6%) and remaining others. FDA approved ascidian compounds mechanism of action along with other compounds status of clinical trials (phase 1 to phase 3) are discussed here in.. These include cyclic peptides and depsipeptides and many different types of aromatic alkaloids essential for the interaction between host and symbiont, and the bacteria are phylogenetically diverse . Many of these metabolites are not produced by the ascidian themselves but by endosymbiotic micro-organisms. Symbiotic bacteria contribute secondary metabolites necessary for defense and the survival of ascidian. About 80 of the currently known secondary metabolites from ascidians are made by symbiotic bacteria . Volume IX, Issue V, MAY/2020 Page No : 115 Mukt Shabd Journal ISSN NO : 2347-3150 There are over 3000 species of ascidians worldwide and in India ratio is 434. Till date only 5% of living ascidian species were studied from <3000 species. Many can tolerate and accumulate heavy metals, although these metals affect the development of embryos and larvae in a dose-dependent fashion. This makes certain species of ascidians useful as indicators of water quality in bioassays for pollutants. In addition, ascidians embryos are also useful as a model to study the neurodevelopment toxicity of different compound. Several families of ascidians accumulate very high levels of vanadium (up to 350 NM) in tissues and blood cells called vanadocytes. These include cyclic peptides and depsipeptides and many different types of aromatic alkaloids. 2. METHOD In India major scientist those are involved in finding tunicates anticancerous activity are VK meenakshi and et al. Dr abdul Jaffar et al from Tamilnadu is also involved in their studies, they find barcode for different gene and identify the animal. All work in India is done on tunicates collected from South coast of India nothing has been done from any other coast. There is plenty of scope of work which could be done from Okha (Gujarat), in which many tunicates are found in ample amount. The physiological function of the accumulated vanadium is presently unclear. It has been suggested that it may be involved in chemical defence. Ascidians are important ecologically due to their invasive potential and adverse effects on native fauna and aquaculture. Fractions were assayed for antitumor and apoptosis inducing properties, revealing many molecules with potential awaiting further research. During 2005 and 2006, marine pharmacology research directed towards the discovery and development of novel antitumor agents was reported in 171 peer-reviewed articles. The organisms yielding these bioactive marine compounds included invertebrate animals, algae, fungi and bacteria. Antitumor pharmacological studies were conducted with Noteworthy is the fact that marine anticancer research was sustained by a global collaborative effort, involving researchers from Australia, Belgium, Benin, Brazil, Canada, China, Egypt, France, Germany, India, Indonesia, Italy, Japan, Mexico, the Netherlands, New Zealand, Panama, the Philippines, Slovenia, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom(UK) and the United States of America. Ascidians have provided a treasure trove of interesting biologically active compounds and much progress has been made in recent years. There are several major challenges in the pipeline from natural product discovery to therapeutic drugs, including the need for sufficient supply of compounds and a lack of knowledge of the biosynthetic pathways or even the responsible organism (symbiotic bacterium or host ascidian) and mechanism of action. Taxonomic identification of ascidians by morphology is also a problem, due to the shortage of expert taxonomists. This can be overcome with DNA barcoding, recently applied to Lissoclinum fragile and four Indian ascidians by sequencing a short segment of mitochondrial DNA coding for subunit 1 of cytochrome C oxidase [1] There is a list of scientists those are working on different ascidian and extracted different compound out of them. Table (1): Ascidians Species along with their compound and effects Scientist Ascidian Effect Compound Reference Species V.K Phallusia Administration of the extract of 2-Piperidinone, Benzeneacetamide, [2] Meenakshi et Nigra Phallusia nigra decreased the Tetradecanoic acid, n- al Savigny, weight, volume of the tumor and Hexadecanoic acid, Phenol 3- increased the percentage pentadecyl, (Z,Z,Z)- phenylmethyl inhibition. An increase on median ester of 6,9,12-Octadecatrienoic survival time, percentage of life acid, (z)-phenylmethyl ester of 9- span, non viable cells and Octadecenoic acid, Cholesterol, decrease in packed cell volume. Cholestan-3-ol and 3-hydroxy- (3a,17a)-Spiro [androst5-ene-17,l’- cyclobutan]-2’-one V.K Ecteinascidia Treatment with ethanolic extract 1-(2-Ethyl-3-cyclohexenyl)ethanol, [3],[4] Meenakshi venui of Ecteinascidia venui showed a (E,E)-methyl ester of 9,12- Meenakshi decrease in tumour volume, Octadecadienoic acid, (E)-methyl packed, viable cells and increase ester of 9-Dodecenoic acid, 9- in median survival time, life span Octadecenal, (Z)6,(Z)9- and nonviable cells of S-180 Pentadecadien-1- ol, (Z,Z)-9,12- tumour Octadecadien-1-ol,13-methyl- Oxacyclotetradecane-2,11-dione, Eicosane, Tetradecyloxirane, (R)-(- )-14-Methyl-8-hexadecyn-1-ol, Nonadecane, 1-Iodo-2- Volume IX, Issue V, MAY/2020 Page No : 116 Mukt Shabd Journal ISSN NO : 2347-3150 methylundecane. V.K Microcosmus Antitumor and n-hexadecanoic acid (21.66%), [5] Meenakshi exasperatus immunomodulatory activity of the tetradecanoic acid (18.98%), ethanolic extract of the simple trichloroacetic acid, hexadecyl ester ascidian Microcosmus (12.57%), 26-Nor-5-cholesten-3á- exasperatus was assessed against ol-25-one (10.70%), 6,9,12- Dalton’s Lymphoma Ascites Octadecatrienoic acid, (DLA) cells. 100% toxicity was phenylmethyl ester, (Z,Z,Z)- observed at a concentration of (8.29%), Cholestan-3-ol (6.95%) 0.80 mg/ml. The extract at 50, and 2-piperidinone, N-[4,bromo-n- 100, 150 butyl]- (3.48%) Satheesh Phallusia The extract of p. Nigra showed 46 metabolite peaks containing [6] Kumar Spp anti tumor activity against HT29 between 234 and 860 m/z in P. Palanisamy et colon cancer and MCF7 breast arabica extract and 68 metabolite al cancer compared to P. Arabica. peaks containing between 170 and 870 m/z in P. nigra extract were reported. Divya T Aplidiam A. multiplicatum contains various Prevailing compounds are 4- [7] Dharan et al Multiplicatum bioactive compounds in ethanolic Butylbenzoic acid, tridec-2-ynyl extract with various activities like ester (41.7%), 5,8,11,14,17- antimicrobial, anti-cancer, Eicosapentaenoic acid, meth diuretic, anti- inflammatory, anti- (20.8%), Pyrrolo [1,2-a] pyrazine- fungal, antioxidant 1,4-dione, hexahy (13.6%), Phenol, 3,5- dimethoxy-,
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