title: Antiproliferative activity of long chain acylated esters of quercetin-3-O-glucoside in hepatocellular carcinoma HepG2 cells.
abstract: Despite their strong role in human health, poor bioavailability of flavonoids limits their biological effects in vivo. Enzymatically catalyzed acylation of fatty acids to flavonoids is one of the approaches of increasing cellular permeability and hence, biological activities. In this study, six long chain fatty acid esters of quercetin-3-O-glucoside (Q3G) acylated enzymatically and were used for determining their antiproliferative action in hepatocellular carcinoma cells (HepG2) in comparison to precursor compounds and two chemotherapy drugs (Sorafenib and Cisplatin). Fatty acid esters of Q3G showed significant inhibition of HepG2 cell proliferation by 85 to 90% after 6 h and 24 h of treatment, respectively. The cell death due to these novel compounds was associated with cell-cycle arrest in S-phase and apoptosis observed by DNA fragmentation, fluorescent microscopy and elevated caspase-3 activity and strong DNA topoisomerase II inhibition. Interestingly, Q3G esters showed significantly low toxicity to normal liver cells than Sorafenib (P < 0.05), a chemotherapy drug for hepatocellular carcinoma. Among all, oleic acid ester of Q3G displayed the greatest antiproliferation action and a high potential as an anti-cancer therapeutic. Overall, the results of the study suggest strong antiproliferative action of these novel food-derived compounds in treatment of cancer.
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada.
authors: Sudhanshu
authors: S
authors: Sudan
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4RN, Canada vrupasinghe@dal.ca.
authors: Hp Vasantha
authors: HV
authors: Rupasinghe
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D053938:DNA Fragmentation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry; D005960:Glucosides; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008856:Microscopy, Fluorescence; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D005227:Fatty Acids; D005419:Flavonoids; D005960:Glucosides; D010671:Phenylurea Compounds; C532085:quercetin 3'-O-glucoside; C016527:isoquercitrin; D009536:Niacinamide; D011794:Quercetin; D000077157:Sorafenib; D053148:Caspase 3; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin
keywords: HepG2 cells; Quercetin-3-O-glucoside; acylation; apoptosis; cancer; caspase-3; cell cycle; chemotherapy; hepatocellular carcinoma; topoisomerase II