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.
Highlights
Cancer mortality rates remain high despite tremendous research efforts and innovative clinical trials with new drug candidates
Many other marine invertebrates with economic importance were characterized concerning their Janus kinase (JAK)/STAT signaling components: SOCS-2 from pearl oyster Pinctada fucata plays a regulatory role against the stimulation [79]; a member of the
STAT4 family was discovered in rock bream (Oplegnathus fasciatus) (RbSTAT4) and its regulation under pathological stimuli was investigated [80]; Janus kinase gene was cloned and characterized from whiteleg shrimp Litopenaeus vannamei [81]. These examples demonstrate the essential function of JAK/STAT like functions in marine invertebrates so that discovery of compounds interfering with these mechanisms from marine organisms should be expected, considering the biochemical warfare described so far between marine organisms related to space and nutrients as we previously reported [9]
Summary
Cancer mortality rates remain high despite tremendous research efforts and innovative clinical trials with new drug candidates. While many compounds were shown to affect nuclear factor-κB (NF-κB) signaling [18], less is known about the impact of natural compounds of STAT-signaling in cancer [19] It appears that STAT signaling in marine organisms is an emerging field of research so that we suggest here to review both the impact of endogenous STAT signaling as an essential function in marine organisms followed by the description of anticancer applications of selected anti-STAT marine compounds. These natural compounds come with outstanding structural diversity and act most likely as physiological regulators with often-unexplored functions They serve as basic templates for the development of drugs with biological properties, through interdisciplinary studies using ecology, biology, pharmacology, and chemistry. Targets of these derivatives include a wide range of diseases, including cancer and compounds, which will be described
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