Biological Effects of Gyrophoric Acid and Other Lichen Derived Metabolites, on Cell Proliferation, Apoptosis and Cell Signaling pathways. (5th January 2022)

• Record Type: Journal Article
• Authors: Mohammadi, Mahshid; Bagheri, Leila; Badreldin, Amr; Fatehi, Pedram; Pakzad, Leila; Suntres, Zacharias; van Wijnen, Andre J.
• Is Part Of: Chemico-biological interactions. Volume 351(2022)
• Publication Date: 2022-01-05
• Subjects: Lichens -- Gyrophoric acid -- Anticancer -- Cardiovascular diseases -- Diabetes -- Mechanism of action -- Secondary metabolite -- Depside -- Topoisomerase -- Proliferation -- Apoptosis -- Cancer cytostatic -- Cytotoxic; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109768
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Secondary metabolites from fungi, algae and lichens have remarkable biological activities as antibiotics, fungicides, antiviral drugs, and cancer therapeutics. This review focuses on the lichen-derived metabolite gyrophoric acid and other select secondary metabolites (e.g., usnic acid, salazinic acid, physodic acid, vulpinic acid ceratinalone, flavicansone, ramalin, physciosporin, tumidulin, atranorin, parmosidone) that modulate a number of cellular pathways relevant to several biomedical diseases and disorders, including cancer, diabetes and cardiovascular disease. We discuss the chemical structure and biochemical activities of gyrophoric acid and other compounds relative to the molecular mechanisms and cellular processes that these metabolites target in a distinct human and rodent cell types. The therapeutic promise of gyrophoric acid and similar lichen derived metabolites is associated with the chemical versatility of these compounds as polyaromatic depsides with functional carboxyl and hydroxyl side-groups that may permit selective interactions with distinct enzymatic active sites. Gyrophoric acid has been examined in a series of studies as an effective anticancer drug because it impinges on topoisomerase 1 activity, as well as causes cell cycle arrest, comprises cell survival, and promotes apoptosis. Because gyrophoric acid has cytostatic properties, its biological roles and possible medicinal utility may extend beyond effects on cancer cells and be relevant to any process that is controlled by cell growth and differentiation. Highlights: Lichen-derived metabolites inhibit clinically relevant cellular pathways. Gyrophoric acid targets many distinct enzymes with low affinity. Gyrophoric acid has cytostatic effects by blocking key cellular pathways. Cytostatic effects of gyrophoric acid may have use in cancer treatment.