Histone Deacetylase Inhibitors from Marine Invertebrates

Abstract

Histone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. The aim of this review is to gather selected studies that report the extraction and identification of marine invertebrate-derived compounds that possess HDACi properties, grouping the producing species according to their taxonomic hierarchy. The molecular, biochemical, and/or physiological aspects, where available, and modes of action of these naturally occurring HDACis will be recapitulated, taking into consideration their possible utilization for the future design of analogs with increased bioavailability and efficacy, less toxicity, and, also, higher isoform selectivity.

Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

“…Among the data collected, psammaplin inhibition of SIRT1 was proven to promote autophagy, as revealed by the increased intracellular formation of acidic vacuolar organelles and the increased expression level of LC3, ATG-3, -5, -7, and -12, as well as beclin-1, the latter being a core component of the class III phosphatidylinositol-3 kinase (PI3K) complex required for autophagosome formation [47]. As a further confirmation of Psammaplin 6), the first one of the phenolic compounds isolated from these Porifera sponges, is a brominated, tyrosine-derived disulfide dimer initially described as an antimicrobial and antifungal compound and subsequently proven to act as an enzymatic inhibitor against topoisomerase, farnesyl protein transferase, chitinase, histone deacetylases, and DNA methyltransferases, thereby also demonstrating anticancer activity [23,[42][43][44][45]. 6), the first one of the phenolic compounds isolated from t Porifera sponges, is a brominated, tyrosine-derived disulfide dimer initially describe an antimicrobial and antifungal compound and subsequently proven to act as an e matic inhibitor against topoisomerase, farnesyl protein transferase, chitinase, his deacetylases, and DNA methyltransferases, thereby also demonstrating anticancer a ity [23,[42][43][44][45].…”

“…Thus, to cite just a few examples, anticancer compounds have been found among the primary and secondary metabolites of starfishes and Mediterranean ascidians [20,21], and extracts or isolated molecules obtained from marine invertebrates have been proven to exert a modulatory effect on collective cell migration, a process at the basis of different biological events such as neoplastic cell metastasization and wound repair [22]. Chemicals with histone deacetylase inhibitory properties, whose wide range of potential biomedical applications is generally acknowledged, have also been extracted and identified in preparations from marine invertebrates [23]. The contribution of marine vertebrates to the food, biomedical, and pharmaceutical sectors has been mainly provided by fish oils, containing long-chain ω−3 polyunsaturated fatty acids, vitamin E, essential aminoacids, and bioactive peptides exerting antioxidant, anti-allergic, and angiotensin-I-converting enzyme (ACE) inhibitory effects.…”

“…applications is generally acknowledged, have also been extracted and identified in preparations from marine invertebrates [23]. The contribution of marine vertebrates to the food, biomedical, and pharmaceutical sectors has been mainly provided by fish oils, containing long-chain ω−3 polyunsaturated fatty acids, vitamin E, essential aminoacids, and bioactive peptides exerting antioxidant, anti-allergic, and angiotensin-I-converting enzyme (ACE) inhibitory effects.…”

“…Foundations 2021, 1, FOR PEER REVIEW 6 the Indo-Pacific ocean and display a smooth, conulose, or tuberculate surface and a hard body with a dense collagenous matrix containing sparse skeletal fibers (Figure 5) [41]. Psammaplin 6), the first one of the phenolic compounds isolated from these Porifera sponges, is a brominated, tyrosine-derived disulfide dimer initially described as an antimicrobial and antifungal compound and subsequently proven to act as an enzymatic inhibitor against topoisomerase, farnesyl protein transferase, chitinase, histone deacetylases, and DNA methyltransferases, thereby also demonstrating anticancer activity [23,[42][43][44][45]. In 2015, Kim et al [46] investigated the antitumor effect of psammaplin A as an inhibitor of sirtuin-1 (SIRT1) histone deacetylase on doxorubicin-resistant MCF-7/adr human breast cancer cells, which are strongly susceptible to the cytotoxic effect of the marine compound.…”

Natural Products in Modern Biology: Ancient Wisdom for Today’s Challenges

“…These enzymes are not only responsible for the maintenance of fundamental cellular processes but are also involved in serious human diseases such as cancer [ 15 ]. For this Special Issue, Luparello et al [ 16 ] summarized studies on marine invertebrate-derived compounds that possess inhibitory properties on histone deacetylases and grouped the producing species according to their taxonomic hierarchy. Particularly, marine habitats represent an eminent source of disparate bioactive secondary metabolites produced by bacteria, plants and animals, whose number is expected to increase rapidly [ 17 ].…”