(1090-A) Oncotherapeutic and gastro-entero-hepatoprotective potential of bioflavonoids: the example of fustin, isolated from the heartwood of Eurasian smoketree (Cotinus coggygria Scop.), Anacardiaceae

Abstract: Introduction
The research on biologically active compounds and the identification of new molecular targets are relevant to the development of drug therapy. The medicinal plant Cotinus coggygria has a high content of polyphenols, including fustin, which is unstudied in preclinical experiments.
Aim
We aim to explore the pharmacological activity of fustin in experimental models with human tumour cell lines and Wistar rats.
Materials and Methods
Fustin was isolated and purified from C. coggygria heartwood by HPLC and NMR-spectroscopy. The in vitro anticancer potential was assessed on human cell lines from breast cancer (MCF7, MDA-MB-231), colon cancer (Colon 26), malignant skin melanoma (A375) and squamous cell skin carcinoma (A431). Gene expression analysis of the ability of fustin to affect mechanisms of apoptosis, migration and adhesion, and block the cell cycle was performed by qRT-PCR. The in vivo study of anti-inflammatory and organoprotective effects of fustin was conducted on rat models of carrageenan-induced acute paw inflammation, indomethacin-induced gastric ulceration, trinitrobenzene sulfonate-induced colitis and paracetamol-induced hepatotoxicity by biochemical analyses, histopathological evaluation and immunohistochemical tests.
Results and Conclusion
The proapoptotic and anti-migratory activity of fustin on breast cancer and colon cancer cells was found. Its anticancer properties are associated with alterations in transcriptional levels of eight genes involved in apoptosis, autophagy and cell cycle control. Fustin suppresses the first phase of acute inflammation, similar to NSAIDs. It exerted a gastro-protective action and reduced the expression of NF-κB. Fustin ameliorated some histopathological parameters of colitis and hepatotoxicity. Some of these effects are due to its antioxidant properties.
Acknowledgements
This study is supported by the Bulgarian National Science Fund, Ministry of Education and Science, Grant number KP-06-N43/6/2020.
Keywords
Smoke-tree heartwood, Cotinus coggygria, Fustin, Cancer cell lines, Wistar Rats