title: Synthesis and biological properties of polyamine modified flavonoids as hepatocellular carcinoma inhibitors.
abstract: A series of polyamine conjugates of flavonoids with a naphthalene motif were synthesized and evaluated for their anti-hepatocellular carcinoma properties using in vitro and in vivo assays. Compound 8a displayed favorable selectivity between hepatocellular carcinoma cells and normal hepatocyte cells, and the combination of 8a with aspirin resulted in additive inhibition of in vitro tumor cell growth and migration. The 8a-aspirin combination also inhibited H22 liver tumor growth and pulmonary metastasis and improved body weight index in animal models. Preliminary mechanistic studies indicated that 8a increased the expression of apoptosis-related proteins such as p-p38, p-JNK, p53 and Bcl-2, an effect that was further amplified by aspirin. Therefore, a cocktail therapy of flavonoid-polyamine conjugates with aspirin has potential use as an antitumor therapy.
authors.affiliation: Key Lab of Natural Medicine and Immune Engineering, Henan University, Henan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Chemistry Department, Henan University, Henan, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Chemistry Department, Henan University, Henan, China. Electronic address: luowen83@henu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.affiliation: Chemistry Department, Henan University, Henan, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Key Lab of Natural Medicine and Immune Engineering, Henan University, Henan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Chemical Biology, Henan University, Henan, China. Electronic address: kfxsq@yahoo.com.cn.
authors.forename: Songqiang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Lab of Natural Medicine and Immune Engineering, Henan University, Henan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hong
authors.affiliation: Chemistry Department, Henan University, Henan, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Chemistry Department, Henan University, Henan, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Su
authors.affiliation: Key Lab of Natural Medicine and Immune Engineering, Henan University, Henan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Lab of Natural Medicine and Immune Engineering, Henan University, Henan, China. Electronic address: wcjsxq@henu.edu.cn.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D001241:Aspirin / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002460:Cell Line / Q000473:pathology; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D009362:Neoplasm Metastasis; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D011073:Polyamines; D001241:Aspirin
keywords: Antitumor; Flavonoids; Polyamine; Synthesis