title: A phenylacetaldehyde-flavonoid adduct, 8-C-(E-phenylethenyl)-norartocarpetin, exhibits intrinsic apoptosis and MAPK pathways-related anticancer potential on HepG2, SMMC-7721 and QGY-7703.
abstract: Norartocarpetin, quercetin and naringenin were found to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation through trapping its phenylacetaldehyde and form their adducts in roast beef patties. Six adducts [8-C- or 6-C-(E-phenylethenyl) flavonoids] formed between phenylacetaldehyde and three flavonoids were detected in roast beef patties by UPLC-MS analyses and compared with their synthetic references. These flavonoid-phenylacetaldehyde adducts were synthesised and further subjected to cytotoxicity tests on three liver cancer cell lines HepG2, SMMC-7721 and QGY-7703. The adduct 8-C-(E-phenylethenyl)norartocarpetin (NARA1) was found to significantly induce cancer cell death with IC50 values about 7 μM. After pre-treating with MAPK and caspase inhibitors, alteration of the cell morphology and cleaved-PARP were detected in liver cancer cell lines administered with NARA1. These data indicated that norartocarpetin could inhibit PhIP formation in roast beef patties and form norartocarpetin-phenylacetaldehyde adducts. The adduct NARA1 has anticancer potential via intrinsic caspase-dependent and cell context-dependent MAPKs pathways.
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, People's Republic of China; Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, People's Republic of China. Electronic address: xu_yang@xmu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D005511:Food Handling; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D000069466:Red Meat / Q000032:analysis
chemical_list: C000609351:8-C-(E-phenylethenyl)-norartocarpetin; D000970:Antineoplastic Agents; D005419:Flavonoids; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D000079:Acetaldehyde; C013192:phenylacetaldehyde
keywords: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); Cytotoxicity effects; Flavonoids; Flavonoid–phenylacetaldehyde adducts; Phenylacetaldehyde