Target identification and mode of action studies on phyllobilins, natural compounds with effects on cancer cells
Final Report Abstract
Phyllobilins, tetrapyrrolic natural substances that result from the breakdown of chlorophyll, are primarily associated with the bright autumn colors of leaves. While the predominant degradation products, the phylloleucobilins, have no color, they can easily be converted into yellow (phylloxanthobilins) and pink (phylloroseobilins) pigments, which also occur naturally and contribute to the autumn color of the leaves. In our previous data, we were able to show interesting bioactivities for these compounds, including that certain phyllobilins can inhibit the growth of cancer cells in vitro and trigger programmed cell death (apoptosis). These findings provide a promising basis for research into their potential as future active ingredients or as ingredients of herbal medicines and plant-based food. In order to position phyllobilins as important plant ingredients rather than by-products of chlorophyll degradation, we have continued our search for these natural compounds and have been able to detect them in important medicinal plants and food, as well as demonstrate their contribution to bioactivities. In order to elucidate the underlying mechanisms of these effects, we have set ourselves the goal of identifying protein targets of phyllobilins in human cells. For un-biased target identification, we have established an improved Yeast-3-Hybrid (Y3H) system to test phyllobilins against human cDNA libraries. The potential of the newly established Y3H screening system was demonstrated by the identification a previously unknown target of a widely used drug. The application of this system to phyllobilins has led to the discovery of several interesting potential targets, which are currently under further investigation. In addition, we used affinity chromatography, in which phyllobilins are coupled to solid supports, to isolate potential targets. These will also be confirmed in the future. Of particular note is the discovery of the cytoskeletal protein actin as a target for both phyllobilins and the structurally related heme-derived tetrapyrroles bilirubin and biliverdin. These advances position phyllobilins as compounds with applications in nutrition, medicine and the environment. Future research will focus on the detailed characterization of the identified interactions and pave the way for innovative uses of these naturally derived molecules.
Publications
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Rising levels of antioxidative phyllobilins in stored agricultural produce and their impact on consumer acceptance. npj Science of Food, 5(1).
Karg, Cornelia A.; Neubig, Christina M.; Roosen, Jutta & Moser, Simone
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Tetrapyrrolic Pigments from Heme‐ and Chlorophyll Breakdown are Actin‐Targeting Compounds. Angewandte Chemie International Edition, 60(41), 22578-22584.
Karg, Cornelia A.; Wang, Shuaijun; Al Danaf, Nader; Pemberton, Ryan P.; Bernard, Denzil; Kretschmer, Maibritt; Schneider, Sabine; Zisis, Themistoklis; Vollmar, Angelika M.; Lamb, Don C.; Zahler, Stefan & Moser, Simone
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A Chlorophyll-Derived Phylloxanthobilin Is a Potent Antioxidant That Modulates Immunometabolism in Human PBMC. Antioxidants, 11(10), 2056.
Karg, Cornelia A.; Parráková, Lucia; Fuchs, Dietmar; Schennach, Harald; Kräutler, Bernhard; Moser, Simone & Gostner, Johanna M.
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Je bunter, desto bioaktiver. Nachrichten aus der Chemie, 70(4), 65-68.
Karg, Cornelia & Moser, Simone
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Phyllobilins – Bioactive Natural Products Derived from Chlorophyll – Plant Origins, Structures, Absorption Spectra, and Biomedical Properties. Planta Medica, 89(06), 637-662.
Karg, Cornelia A.; Taniguchi, Masahiko; Lindsey, Jonathan S. & Moser, Simone
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Using the yeast three-hybrid system for the identification of small molecule-protein interactions with the example of ethinylestradiol. Biological Chemistry, 403(4), 421-431.
Wang, Pengyu; Klassmüller, Thomas; Karg, Cornelia A.; Kretschmer, Maibritt; Zahler, Stefan; Braig, Simone; Bracher, Franz; Vollmar, Angelika M. & Moser, Simone
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Structural Characterization, and Antioxidative and Anti-inflammatory Activities of Phylloxanthobilins in Tropaeolum majus, a Plant with Relevance in Phytomedicine. Planta Medica, 90(07/08), 641-650.
Frei, Patricia; Nadegger, Christian; Vollmar, Angelika M.; Müller, Thomas & Moser, Simone
