Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: the role of glutathione.
Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: the role of glutathione.
复制标题
DOI：
10.1016/j.taap.2011.08.004
复制
发表时间：
2012-01-01
影响因子：
3.8
通讯作者：
Day BJ
中科院分区：
文献类型：
--
作者：
Brechbuhl HM;Kachadourian R;Min E;Chan D;Day BJ
我们假设类黄酮诱导的谷胱甘肽（GSH）通过多药耐药蛋白（MRPs）和随后的细胞内GSH耗尽流出是一种可行的机制，使癌细胞对化疗敏感。在暴露于化疗剂多柔比星（DOX）的人非小细胞肺癌细胞系中，使用白杨素（5-25 μM）诱导的GSH流出证实了这一概念。白杨素处理导致显著和持续的细胞内GSH耗竭，并且四种癌细胞类型中的GSH酶网络可预测白杨素诱导的细胞内GSH耗竭的严重程度。基因表达数据表明，基础MRP 1，MRP 3和MRP 5的表达和总GSH流出白杨素曝光前后呈正相关。在所有四种细胞系中，与单独DOX处理72小时相比，用白杨素（5-30 μM）和DOX（0.025-3.0 μM）共处理细胞72小时显著增强了细胞对DOX的敏感性。与白杨素和DOX共同处理相比，单独用DOX处理的细胞的IC 50值的最大降低在A549细胞中为43%，在H157和H1975细胞中为47%，在H460细胞中为78%。Doxin与DOX协同作用以诱导癌细胞死亡。这种方法可以允许使用较低的浓度和/或使癌细胞对通常对治疗有抗性的药物敏感。
We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5–25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 hours with chrysin (5–30 μM) and DOX (0.025–3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC50 values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy.
登录
查看更多内容
影响因子：
3.9
作者：
Grant, Caroline E.;Gao, Mian;Deeley, Roger G.
通讯作者：
Deeley, Roger G.
影响因子：
3.5
作者：
Lee, Chang Ki;Son, Seung Hwa;Chung, Won Yoon
通讯作者：
Chung, Won Yoon
影响因子：
7.4
作者：
Kachadourian, Remy;Day, Brian J.
通讯作者：
Day, Brian J.
DOI：
10.1093/jnci/89.23.1789
发表时间：
1997-12-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Bailey, HH;Ripple, G;Wilding, G
通讯作者：
Wilding, G
影响因子：
2.4
作者：
Klein R;Brown D;Turnley AM
通讯作者：
Turnley AM