Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma

Jong Cheon Joo, Jung Hoo Hwang, Eunbi Jo, Young Rang Kim, Dae Joon Kim, Kyung Bok Lee, Soo Jung Park, Ik Soon Jang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12211-12224
Number of pages14
JournalOncotarget
Volume8
Issue number7
DOIs
StatePublished - 2017

Keywords

  • Apoptosis
  • CAV1
  • Cordycepin
  • Foxo3a
  • JNK

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma'. Together they form a unique fingerprint.

Cite this