Celastrol induces apoptosis in gefitinib-resistant non-small cell lung cancer cells via caspases-dependent pathways and Hsp90 client protein degradation.
Celastrol induces apoptosis in gefitinib-resistant non-small cell lung cancer cells via caspases-dependent pathways and Hsp90 client protein degradation.
复制标题
DOI：
10.3390/molecules19033508
复制
发表时间：
2014-03-21
期刊：
影响因子：
--
通讯作者：
Leung EL
中科院分区：
文献类型：
--
作者：
Fan XX;Li N;Wu JL;Zhou YL;He JX;Liu L;Leung EL
雷公藤红素是从雷公藤中提取的一种三萜类化合物，具有多种生物活性。虽然在这些活性中，其抗癌作用引起了最多的关注，但雷公藤红素对吉非替尼耐药的非小细胞肺癌（NSCLC）细胞的作用尚不清楚。在这里，我们检查了雷公藤红素在三种不同的NSCLC细胞系中的效力。我们探讨了其在两个吉非替尼耐药的NSCLC细胞系（H1650和H1975）中的治疗机制。我们的数据表明雷公藤红素以剂量和时间依赖性方式发挥其凋亡作用。此外，雷公藤红素处理后线粒体膜电位逐渐丧失，Bax/Bcl-2比值增加，这两者都是线粒体膜完整性的指标。虽然caspase被激活，但用pan-caspase抑制剂处理可部分抑制凋亡水平。此外，测量Hsp 90客户蛋白EGFR和AKT的蛋白水平。有趣的是，在雷公藤红素处理后，两种客户蛋白都显著下调。综上所述，我们的数据表明雷公藤红素可能被开发为通过半胱天冬酶依赖性途径和Hsp 90客户蛋白降解诱导细胞凋亡来治疗吉非替尼耐药NSCLC的有前途的药物。
Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is not clearly known. Here, we examined the potency of celastrol in three different NSCLC cell lines. We explored its treatment mechanism in two gefitinib-resistant NSCLC cell lines (H1650 and H1975). Our data demonstrated that celastrol exerted its apoptotic effect in a dose- and time-dependent manner. Also, the mitochondria membrane potential was gradually lost and the ratio of Bax/Bcl-2 increased after the treatment of celastrol, both of which are indicators of mitochondria membrane integrity. Although the caspases were activated, the treatment with pan-caspase inhibitor could partially inhibit the level of apoptosis. Moreover, the protein level of Hsp90 client proteins, EGFR and AKT, was measured. Interestingly, both client proteins were remarkably down-regulated after the treatment of celastrol. Taken together, our data showed that celastrol may be developed as a promising agent for treating gefitinib-resistant NSCLCs by inducing apoptosis through caspase-dependent pathways and Hsp90 client protein degradation.
登录
查看更多内容
NF-κB抑制剂雷公藤红素可增强藤黄酸对口腔鳞状细胞癌的抗癌作用
影响因子：
3.8
作者：
He D;Xu Q;Yan M;Zhang P;Zhou X;Zhang Z;Duan W;Zhong L;Ye D;Chen W
通讯作者：
Chen W
影响因子：
5.7
作者：
Kim, Hwang-Phill;Han, Sae-Won;Kim, Tae-You
通讯作者：
Kim, Tae-You
影响因子：
4
作者：
Maddika, S;Booy, EP;Los, M
通讯作者：
Los, M
精神分裂素通过抑制MAPK家族的激活和线粒体依赖性途径来保护原发性大鼠皮质细胞培养物免受谷氨酸诱导的凋亡。
DOI：
10.3390/molecules18010354
发表时间：
2012-12-27
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lee MS;Chao J;Yen JC;Lin LW;Tsai FS;Hsieh MT;Peng WH;Cheng HY
通讯作者：
Cheng HY
影响因子：
5
作者：
Kim, Dae Yong;Park, Jung Won;Ro, Jai Youl
通讯作者：
Ro, Jai Youl