title: p-terphenyl derivatives from the mushroom Thelephora aurantiotincta suppress the proliferation of human hepatocellular carcinoma cells via iron chelation.
abstract: A novel 2',3'-dihydroxy-p-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity, was isolated. This study investigated the underlying basis of the cytotoxicity of 2',3'-dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl(2) significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure-activity relationship study using newly synthesized p-terphenyl derivatives revealed that o-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe(2+) chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that the TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl(2). Thus, it was concluded that Fe(2+) chelation occurs upstream in the pivotal pathway of 2',3'-dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.
authors: Department of Nutrition, Faculty of Health Science, Aomori University of Health and Welfare, Mase 58-1, Hamadate, Aomori 030-8505, Japan. t_norikura@auhw.ac.jp
authors: Toshio
authors: T
authors: Norikura
authors: Kenshu
authors: K
authors: Fujiwara
authors: Takanori
authors: T
authors: Yanai
authors: Yusuke
authors: Y
authors: Sano
authors: Takuto
authors: T
authors: Sato
authors: Takayuki
authors: T
authors: Tsunoda
authors: Keisuke
authors: K
authors: Kushibe
authors: Akiko
authors: A
authors: Todate
authors: Yae
authors: Y
authors: Morinaga
authors: Kunihisa
authors: K
authors: Iwai
authors: Hajime
authors: H
authors: Matsue
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015394:Molecular Structure; D013730:Terphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D013730:Terphenyl Compounds; C562008:thelephantin O; D007501:Iron