Cancer chemopreventive properties of orally bioavailable flavonoids - Methylated versus unmethylated flavones
Cancer chemopreventive properties of orally bioavailable flavonoids - Methylated versus unmethylated flavones
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DOI：
10.1016/j.bcp.2006.12.028
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Walle, U. Kristina
中科院分区：
文献类型：
--
作者：
Walle, Thomas;Ta, Nga;Walle, U. Kristina
口服生物利用度差一直是成功使用膳食类黄酮作为癌症化学预防剂的主要限制。在这项研究中，我们研究了完全甲基化的黄酮作为有前途的改进剂。在人口腔SCC-9癌细胞中，5，7-二甲氧基黄酮和5，7，4 ′-三甲氧基黄酮都是比相应的未甲基化类似物白杨素和芹菜素强10倍的细胞增殖抑制剂（IC 50值5-8 μ M）。流式细胞术表明，甲基化的黄酮逮捕SCC-9细胞在G1期与S期的同时减少，显着不同的非甲基化的类似物，这促进G2/M期逮捕。这两种甲基化化合物都抑制了另外两种癌细胞系的增殖，对两种永生化正常细胞系的影响很小。额外的黄酮结构的检查表明，甲基化黄酮一般具有抗增殖特性。最后，我们证明了5，7-二甲氧基黄酮，与其未甲基化的类似物白杨素相比，吸收良好，具有较高的口服生物利用度以及在大鼠体内的组织蓄积。因此，完全甲基化的黄酮似乎具有作为癌症化学预防/化学治疗剂的巨大潜力，特别是在口腔癌中。(c)2007爱思唯尔公司All rights reserved.
Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the human oral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were both 10 times more potent inhibitors of cell proliferation (IC50 values 5-8 mu M) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines with very little effect on two immortalized normal cell lines. Examination of additional flavone structures indicated that methylated flavones in general have antiproliferative properties. Finally, we demonstrated that 5,7-dimethoxyflavone, in contrast to its unmethylated analog chrysin, was well absorbed and had high oral bioavailability as well as tissue accumulation in vivo in the rat. Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents, in particular in oral cancer. (c) 2007 Elsevier Inc. All rights reserved.