Signal Transducers and Activators of Transcription (STAT) Regulatory Networks in Marine Organisms: From Physiological Observations towards Marine Drug Discovery

Abstract

Part of our ocean’s richness comes from its extensive history of supporting life, resulting in a highly diverse ecological system. To date, over 250,000 species of marine organisms have been identified, but it is speculated that the actual number of marine species exceeds one million, including several hundreds of millions of species of marine microorganisms. Past studies suggest that approximately 70% of all deep-sea microorganisms, gorgonians, and sea sponges produce secondary metabolites with anti-cancer activities. Recently, novel FDA-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. Despite the fact that many marine natural products have been shown to possess a good inhibition potential against most of the cancer-related cell signaling pathways, only a few marine natural products have been shown to target JAK/STAT signaling. In the present paper, we describe the JAK/STAT signaling pathways found in marine organisms, before elaborating on the recent advances in the field of STAT inhibition by marine natural products and the potential application in anti-cancer drug discovery.

Marine Natural Products from Indonesian Waters

“…To date, eight marine-derived natural products [7,8,9,10] have been recorded as approved drugs, of which seven molecules have been used to date. (–)-Ecteinascidin 743 (Yondelis ® ) was derived directly from the Caribbean ascidian Ecteinascidia turbinata (the true producer was recently established as γ-proteobacterial endosymbiont Candidatus endoecteinascidia frumentensis [11]).…”

Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer

“…Used empirically in traditional medicine for thousands of years without fully knowing their mechanisms of action, natural products from marine or terrestrial organisms feature a wide variability of chemical structures that modulate a wide range of biological effects (Cerella et al 2014;Morceau et al 2015;Schnekenburger et al 2014Schnekenburger et al , 2015Schumacher et al 2011). These compounds act on a number of therapeutic targets, including processes involved in cancer development and progression (Gaascht et al 2010;Lee et al 2015;Muller et al 2015;Sawadogo et al 2012Sawadogo et al , 2015Teiten et al 2013). Among the vast natural chemical library, we can note isolated plant substances, such as curcumin (Teiten et al 2010(Teiten et al , 2011, aurones (Zwergel et al 2012), plumbagin (Gaascht et al 2014) and fungal secondary metabolites embellicines (Ebrahim et al 2013), which were recently investigated for their chemopreventive and anticancer properties.…”

Quorum Sensing Inhibition by Marine Bacteria

“…Research about the biotechnological potential of marine organisms (comprising corals, sponges, algae and bacteria) is limited and few marine-derived products are in clinical use. Examples of products include, cytarabine (Cytosar-U ® , 1969; Depocyt ® ; cancer and leukemia), vidarabine (Vira-A ® , 1979; antiviral—herpes simplex virus), ziconotide (Prialt ® , 2004; severe chronic pain), omega-3-acid ethyl esters (Lovaza ® , 2004; hypertriglyceridemia), eribulin mesylate (Halaven ® , 2010; cancer: metastatic breast cancer), brentuximab vedotin (Adcetris ® , 2011; cancer: anaplastic large T-cell systemic malignant lymphoma, Hodgkin’s disease), trabectedin (Yondelis ® , 2015; cancer: soft tissue sarcoma and ovarian cancer) and plitidepsin (Aplidin ® , 2018; cancer: multiple myeloma, leukemia, lymphoma) [71,72,73,74,75]. The first seven are currently Food and Drug Administration (FDA) approved marine-derived drugs, and the last one was approved by the European Agency [70,74,76] (Figure 4).…”