Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells
Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells
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DOI：
10.2741/2199
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Dou, Q. Ping
中科院分区：
文献类型：
--
作者：
Chen, Di;Chen, Marina S.;Dou, Q. Ping
富含蔬菜和水果的饮食与降低癌症风险有关。然而，涉及的机制是未知的。我们以前曾报道过芹菜素类黄酮能抑制蛋白酶体活性，诱导肿瘤细胞凋亡。为了进一步研究结构-蛋白酶体-抑制活性的关系，我们选择并测试了五种膳食黄酮，包括毛地黄黄酮，芹菜素，白杨素，柚皮素和圣草酚。结果表明，这5个化合物对20 S蛋白酶体和肿瘤细胞的抑制和诱导活性顺序为：（1）毛地黄黄酮>芹菜素>白杨素;（2）芹菜素>>柚皮素，毛地黄黄酮>>圣草酚。因此，具有羟基化B环和/或不饱和C环的黄酮类化合物是天然有效的蛋白酶体抑制剂和肿瘤细胞凋亡诱导剂。此外，芹菜素和木犀草素都不能抑制蛋白酶体和诱导非转化的人自然杀伤细胞凋亡。这一发现可能为临床观察到的水果和蔬菜的癌症预防作用提供分子基础。
Diet high in vegetables and fruits has been associated with reduced cancer risk. However, the involved mechanisms are unknown. Previously, we reported that the dietary flavonoid apigenin could inhibit the proteasome activity and induce apoptosis in tumor cells. To further investigate the structure-proteasome-inhibitory activity relationships, we chose and tested five dietary flavonoids, including luteolin, apigenin, chrysin, naringenin and eriodictyol. We found that the order of inhibitory potencies and apoptosis-inducing potencies of these five compounds in 20S purified proteasome and tumor cells was: ( 1) luteolin > apigenin > chrysin, and ( 2) apigenin >> naringenin, and luteolin >> eriodictyol. Therefore, flavonoids with hydroxylized B ring and/or unsaturated C ring are natural potent proteasome inhibitors and tumor cell apoptosis inducers. Furthermore, neither apigenin nor luteolin could inhibit the proteasome and induce apoptosis in non-transformed human natural killer cells. This finding may provide a molecular basis for the clinically observed cancer-preventive effects of fruits and vegetables.