Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cordycepin Resensitizes T24R2, Cisplatin-resistant Human Bladder Cancer Cell, to Cisplatin by Inhibiting the AKT-mediated Ets-1 Activation

Version 1 : Received: 21 January 2020 / Approved: 22 January 2020 / Online: 22 January 2020 (09:18:20 CET)

A peer-reviewed article of this Preprint also exists.

Oh, S.-S.; Lee, K.W.; Madhi, H.; Jeong, J.-W.; Park, S.; Kim, M.; Lee, Y.; Han, H.-T.; Hwangbo, C.; Yoo, J.; Kim, K.D. Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription. Int. J. Mol. Sci. 2020, 21, 1710. Oh, S.-S.; Lee, K.W.; Madhi, H.; Jeong, J.-W.; Park, S.; Kim, M.; Lee, Y.; Han, H.-T.; Hwangbo, C.; Yoo, J.; Kim, K.D. Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription. Int. J. Mol. Sci. 2020, 21, 1710.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1710
DOI: 10.3390/ijms21051710

Abstract

Resistance of tumor cells to anticancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin inT24R2, a derived T24 cell line. Treatment with cordycepin or cisplatin (2 g/ml) alone could not induce cell death of T24R2, but combination treatment of these drugs significantly induced apoptosis of the cells through mitochondrial pathway including depolarization of mitochondrial membrane, decrease of anti-apoptotic proteins, Bcl-2, Bcl-xL, and Mcl-1, and increase of pro-apoptotic proteins, Bak and Bax. . High expression of MDR1 was the cause of cisplatin resistance in T24R2, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on a transcription factor, Ets-1, in T24R2 cells. Although there is a correlation between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr-38 phosphorylated form (pThr-38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 level through inhibition of AKT, which reduced MDR1 transcription and induced the resensitization of T24R2 to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of anti-cancer drug resistant patients.

Subject Areas

Cordycepin; Cisplatin-resistance; Resensitization; MDR1; Ets-1; AKT

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.