Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma.
Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma.
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DOI：
10.18632/oncotarget.14661
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发表时间：
2017-02-14
期刊：
影响因子：
--
通讯作者：
Jang IS
中科院分区：
文献类型：
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作者：
Joo JC;Hwang JH;Jo E;Kim YR;Kim DJ;Lee KB;Park SJ;Jang IS
叉头转录因子 (Foxo3a) 是 JNK 诱导的肿瘤抑制的下游效应子。然而，目前尚不清楚caveolin-1（CAV1）介导的JNK/Foxo3a通路是否参与癌细胞凋亡。我们发现虫草素上调 CAV1 表达，并伴有 JNK 磷酸化（p-JNK）和随后的 Foxo3a 易位到细胞核中，导致 Bax 蛋白表达上调。此外，我们发现CAV1过表达上调p-JNK，而CAV1 siRNA下调p-JNK。此外，特异性 JNK 抑制剂 SP600125 显着增加 Foxo3a 磷酸化，从而下调 Foxo3a 易位到细胞核中，表明 CAV1 介导 Foxo3a 的 JNK 调节。 Foxo3a siRNA下调Bax蛋白并减弱A549细胞凋亡，表明CAV1介导的JNK/Foxo3a通路诱导A549肺癌细胞凋亡。虫草素显着降低了裸鼠的肿瘤体积。综上所述，这些结果表明虫草素可促进 CAV1 上调，从而增强 JNK/Foxo3a 信号通路激活，诱导肺癌细胞凋亡，并支持其作为肺癌治疗剂的潜力。
Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.