Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549.
Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549.
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DOI：
10.1371/journal.pone.0079201
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang XH
中科院分区：
文献类型：
--
作者：
Chen XM;Bai Y;Zhong YJ;Xie XL;Long HW;Yang YY;Wu SG;Jia Q;Wang XH
汉黄芩素（Wogonin）是一种植物单体化合物，具有抑制肿瘤细胞生长和诱导肿瘤细胞凋亡的作用。本研究探讨汉黄芩素对A549细胞的凋亡诱导活性及其作用机制。结果表明汉黄芩素对A549细胞活力有明显的抑制作用。汉黄芩素诱导的凋亡蛋白变化包括XIAP和Mcl-1表达减少，裂解PARP表达增加，AIF和细胞色素C释放增加。Western blot分析显示，在肿瘤发生发展过程中起重要作用的c-Myc/Skp 2和HDAC 1/HDAC 2通路活性降低。定量PCR检测到c-Myc mRNA水平升高，蛋白水平降低。还分析了参与c-Myc泛素依赖性降解的Fbw 7 α、GSK 3 β和Thr 58-Myc的蛋白水平。汉黄芩素作用后，Fbw 7 α和GSK 3 β表达下降，Thr 58-Myc表达增加。然而，MG 132不能阻止c-Myc降解。本研究结果表明汉黄芩素具有多种抗癌作用，与c-Myc，SKP 2，HDAC 1和HDAC 2的降解有关。其诱导细胞凋亡的能力独立于Fbw 7 α，这表明其可能用于与Fbw 7缺陷相关的耐药性癌症。需要进一步的研究来确定哪些途径与c-Myc和Fbw 7 α逆转相关，以及c-Myc的Thr 58磷酸化是否依赖于GSK 3 β。
Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. The present study examined the apoptosis-inducing activity and underlying mechanism of action of wogonin in A549 cells. The results showed that wogonin was a potent inhibitor of the viability of A549 cells. Apoptotic protein changes detected after exposure to wogonin included decreased XIAP and Mcl-1 expression, increased cleaved-PARP expression and increased release of AIF and cytotchrome C. Western blot analysis showed that the activity of c-Myc/Skp2 and HDAC1/HDAC2 pathways, which play important roles in tumor progress, was decreased. Quantitative PCR identified increased levels of c-Myc mRNA and decreased levels of its protein. Protein levels of Fbw7α, GSK3β and Thr58-Myc, which are involved in c-Myc ubiquitin-dependent degradation, were also analyzed. After exposure to wogonin, Fbw7α and GSK3β expression decreased and Thr58-Myc expression increased. However, MG132 was unable to prevent c-Myc degradation. The present results suggest that wogonin has multiple anti-cancer effects associated with degradation of c-Myc, SKP2, HDAC1 and HDAC2. Its ability to induce apoptosis independently of Fbw7α suggests a possible use in drug-resistance cancer related to Fbw7 deficiency. Further studies are needed to determine which pathways are related to c-Myc and Fbw7α reversal and whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.
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影响因子：
64.8
作者：
Inuzuka, Hiroyuki;Shaik, Shavali;Onoyama, Ichiro;Gao, Daming;Tseng, Alan;Maser, Richard S.;Zhai, Bo;Wan, Lixin;Gutierrez, Alejandro;Lau, Alan W.;Xiao, Yonghong;Christie, Amanda L.;Aster, Jon;Settleman, Jeffrey;Gygi, Steven P.;Kung, Andrew L.;Look, Thomas;Nakayama, Keiichi I.;DePinho, Ronald A.;Wei, Wenyi
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21.3
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5.3
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
Lin HK