Antitumor Effects of Sea Hare-Derived Compounds in Cancer

Abstract

Sea hares (family Aplysiidae) are a rich source of bioactive substances. Especially, over the past 40 years, the genera Aplysia and Dolabella have afforded numerous bioactive secondary metabolites that exhibit antitumor activity. For example, the depsipeptide dolastatin 10 and its analogue are currently in cancer clinical trials. Meanwhile, the chemical probe approach has revealed that the antitumor macrolide aplyronine A inhibits microtubule assembly in association with actin. This article highlights the recent findings regarding the chemical biology of antitumor and antineoplastic compounds from sea hares, as well as molecules that have been discovered and characterized after 2000.Keywords Antitumor · Sea hare · Aplysia · Antitumor · Actin-deplymerization · Cytotoxicity · Tubulin IntroductionSea hares, which belong to the opisthobranch group of mollusks (clade Aplysiomorpha), are shell-less, slow-moving benthic marine mollusks [1]. The order Anaspidea includes two families, Akeridae and Aplysiidae [2]. Almost all chemical studies have focused on Aplysiidae specimens. The family Aplysiidae includes nine genera, Aplysia (Linnaeus 1767), Bursatella (Blainville 1817), Dolabella (Lamarck 1801), Dolabrifera (Gray 1847), Notarchus (Cuvier 1817), Petalifera (Gray 1847), Phyllaplysia (Fischer 1872), Syphonota (Adams 1854), and Stylocheilus (Gould 1852). Sea hares are herbivorous, and are typically found on seaweed in shallow water. They are not eaten by other marine animals and have been postulated to contain chemical defense substances. The poisonous properties of sea hare secretions were known in Roman times. In addition, sea hares release ink from their ink glands, which deter predators. This ink acts as a screen, while at the

Bioactive Compounds from Marine Heterobranchs

“…A. kurodai has been widely studied over the years, containing a series of compounds that include polyketide macrolides, halogenated and brominated mono- and di-terpenes, brominated sesquiterpenoids, sterols, alkaloids, peptides, and others [ 1 , 2 ]. Aplyronines A–H ( 191,290–293 ) are polyketide macrolides found in Pacific specimens along with aplaminal ( 294 ), some of them being tested in antitumor clinical trials [ 46 , 652 , 653 , 654 , 655 , 656 ]. For human HeLa-S3 cancer cells, IC 50 values were 0.5 nM for aplyronine A ( 191 ), 3 nM for aplyronine B ( 290 ), 22 nM for aplyronine C ( 291 ), 0.08 nM for aplyronine D ( 292 ), and 10 nM for aplyronine H ( 293 ) [ 653 , 657 , 658 ].…”

“…In fact, marine organisms are still considered an underexplored source of NPs, displaying specific biological activities, with biomedically interesting applications to be potentially used as drugs [ 2 , 5 , 6 , 8 , 10 , 29 , 30 , 31 , 44 ]. Many compounds found in heterobranchs are also promising drugs and are being tested under clinical trials [ 36 , 43 , 45 , 46 ]. However, as far as we know, there has not yet been a comprehensive published review on the bioactivity of MNPs from heterobranch molluscs, despite the fact that this is one of the most chemodiverse invertebrate groups [ 2 , 4 ].…”

Terpenoids in Marine Heterobranch Molluscs

“…For heterobranchs, their pharmacological potential in drug discovery is remarkable. Promising heterobranch compounds include several aplyronines and dolastatins from the anaspidean Dolabella auricularia and bursatellanins from Bursatella leachii, kahalalides from the sacoglossan Elysia rufescens, jorumycin from the doridacean Jorunna funebris, ulapualides from Hexabranchus sanguineus, and kabiramide from Hexabranchus sp, some of them being examples of highly effective compounds against tumors in clinical trials [39,[41][42][43]. [3,19,20].…”

Redescription of the Cephalaspidea gastropod Atys jeffreysi (Weinkauff, 1866) (Haminoeidae), with a discussion on the phylogenetic affinities of the Mediterranean species of the genus

“…Haminoeidae is no exception as defensive chemicals such as polypropionates, dubbed Haminols, have been isolated from species of Haminoea (Cimino et al 1991;Marin et al 1999;Cutignano et al 2007;Nuzzo et al 2015) and the cytotoxic polypropionate Nalodionol has been isolated from Smaragdinella calyculata (Broderip & Sowerby, 1829) (Szabo et al 1996). Polypropionates have gained a lot of interest because of their properties as potential anticancer, antibiotic, antiparasitic and imunorepressing compounds (Davies-Coleman and Garson 1998;Pelttari et al 2002;Chênevert et al 2003;Kigoshi and Kita 2015). Additionally, alkylphenols and alkylcatechols have been isolated from Haloa japonica (Pilsbry, 1895b) (as Haminoea callidegenita; Spinella et al 1998;Marin et al 1999;Izzo et al 2000), which are interesting molecules for biomedicine as they seem to have cytotoxic antibiotic and DNA strand cutting abilities (Izzo et al 2000).…”