A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner |
| |
Authors: | Rana Ahmed Youness Reem Amr Assal Shahira Mohamed Ezzat Mohamed Zakaria Gad Amira Abdel Motaal |
| |
Institution: | 1. Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt;2. rana.ahmed-youness@guc.edu.eg rana.youness21@gmail.com;4. Department of Pharmacology and Toxiciology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt;5. Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza, Egypt;6. Department of Pharmacognosy, Faculty of Pharmacy, Modern Sciences and Arts University, 6th of October, Egypt;7. Department of Biochemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt;8. Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia |
| |
Abstract: | AbstractThis study focused on studying the impact of flavonoids isolated from Cleome droserifolia on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from C. droserifolia namely, Isorhamnetin-3-O-β-D-glucoside (1), Quercetin-3`-methoxy-3-O-(4``-acetylrhamnoside)-7-O-α-rhamnoside (2), and Kaempferol-4`-methoxy-3,7-O-dirhamnoside (3). They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. (2) Showed the most potent effects in halting HCC tumorigenic activity (IC50=36?±?1.70?µM) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by (2) was observed. Moreover, attenuation of (2) mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of C. droserifolia in harnessing HCC progression in-vitro with a possible contribution of TP53/miR-15a/miR-16. |
| |
Keywords: | Cleome droserifolia flavonoids hepatocelllar carcinoma TP53 miR-15a miR-16 Quercetin |
|
|