Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition.

The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.

An integrated in vitro approach on the enzymatic and antioxidant mechanisms of four commercially available essential oils (Copaifera officinalis, Gaultheria fragrantissima, Helichrysum italicum, and Syzygium aromaticum) traditionally used topically for their anti-inflammatory effects.

Introduction: Despite the increasing number of essential oils being reported on their potential therapeutic effects, some remain relatively unknown on their biological properties. That is the case of the essential oils obtained from copaiba (Copaifera officinalis L.), wintergreen (Gaultheria fragrantissima Wall.), everlasting (Helichrysum italicum (Roth) G.Don) and clove (Syzygium aromaticum (L.) Merr. & L.M.Perry), commonly labelled as being useful on the amelioration of conditions with an inflammatory background. Methods: To further broaden the current knowledge on the four essential oils, commercially available samples were approached on their effects upon a series of mediators that are involved on the inflammatory and oxidative response, both through in vitro cell-free and cell-based assays (5-lipoxygenase activity, lipid peroxidation, free radical and nitric oxide radical scavenging properties or tyrosinase inhibition). Results: The four oils proved to be active at some of the concentrations tested in most of the performed assays. Significant differences were found between the essential oils, S. aromaticum proving to tbe the most active, followed by G. fragrantissima against 5-lipoxygenase (5-LOX) and linoleic acid peroxidation, proving their potential use as antioxidants and anti-inflammatory agents. In fact, the IC50 value of S. aromaticum in the 5-LOX assay was 62.30 µg mL-1. Besides S. aromaticum efficiently scavenged superoxide radicals generated by xanthine/xanthine oxidase, displaying an IC50 value of 135.26 µg mL-1. The essential oil obtained from H. italicum exhibited a significant decrease in the nitric oxide levels on BV-2 cells, showing its potential as a cytoprotective agent against toxic damage. Copaiba oil ranked first as the most potent tyrosinase inhibitor, exhibiting an IC50 98.22 µg mL-1. Conclusion: More studies are needed to describe the essential oils properties, but these results confirm the potential of these essential oils as anti-inflammatory and antioxidant agents.