p-Terphenyl Derivatives from the Mushroom Thelephora aurantiotincta Suppress the Proliferation of Human Hepatocellular Carcinoma Cells via Iron Chelation

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• 作者：Toshio Norikura ; Kenshu Fujiwara ; Takanori Yanai ; Yusuke Sano ; Takuto Sato ; Takayuki Tsunoda ; Keisuke Kushibe ; Akiko Todate ; Yae Morinaga ; Kunihisa Iwai ; Hajime Matsue
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2013
• 出版时间：February 13, 2013
• 年：2013
• 卷：61
• 期：6
• 页码：1258-1264
• 全文大小：401K
• 年卷期：v.61,no.6(February 13, 2013)
• ISSN：1520-5118

文摘

A novel 2鈥?3鈥?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鈥?3鈥?dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl₂ significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure鈥揳ctivity 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 Fe²⁺ 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 FeCl₂. Thus, it was concluded that Fe²⁺ chelation occurs upstream in the pivotal pathway of 2鈥?3鈥?dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.

Keywords:

2鈥?3鈥?dihydroxy-p-terphenyl derivatives; Thelephora aurantiotincta; thelephantin O; structure鈭抋ctivity relationships; cytotoxicity; Fe²⁺ chelation