Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells

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• 作者：Zhang ; Ting ; Chen ; Xiaolan ; Qu ; Lingbo ; Wu ; Jinglan ; Cui ; Ran ; Zhao ; Yufen
• 关键词：Chrysin ; Phosphate ester of chrysin ; Hela cell line ; Proliferation ; Differentiation ; Apoptosis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2004
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：December 1, 2004
• 卷：12
• 期：23
• 页码：6097-6105
• 文件大小：427 K

摘要

To improve the biological activities of chrysin (CR), we synthesize Diethyl Chysin-7-yl phosphate (CPE: C₁₉H₁₉O₇P) and tetraethyl bis-phosphoric ester of chrysin (CP: C₂₃H₂₈O₁₀P₂) through a simplified Atheron芒芒芒Todd reaction. The interactions of the CR and CPE with lysozyme were explored by electrospray ionization mass spectrometry (ESI) and fluorescence spectrometry method. Experimental results indicate that CPE could form the noncovalent compound with lysozyme, while the interaction of the CR with lysozyme was not detected. In addition, whether and how the compounds CPE and CP affect proliferation and apoptosis in human cervical cancer Hela cells were investigated. Moreover, the effects of CPE and CP in Hela cells were compared with that of the nonmodified CR compound. The Hela cells were co-cultured with CR, CP, and CPE as experimental groups, respectively, and corresponding control groups treated without CR, CP, and CPE. The proliferation and apoptosis were detected using MTT assay, HCl denatured-methyl green-pyronin staining, PCNA immunohistochemistry and TUNEL techniques. The cell growth IC₅₀, relative absorbance (RA), proliferating index (PI), PCNA-IR (immunoreactivity IR) integration value (IV), and apoptosis index (AI) were calculated and their correlation was analyzed in each group. The results show that all CR, CP, and CPE could inhibit proliferation and induce apoptosis in Hela cells. Moreover, the effects of CP and CPE were more potent than that of CR. The CP and CPE were proved to be a kind of stronger apoptosis inducers than nonphosphated CR. There was a negative correlation between proliferation and apoptosis. In conclusion, the CR, CP, and CPE could effectively inhibit growth by down-regulated expression of PCNA, and induce apoptosis in Hela cells. The efficiency of the modified CP and CPE preceded nonmodified CR compounds. The CP and CPE may be a new potential anti-cancer drug for therapy of human cervical carcinoma.