Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-κB signaling pathway

Authors

Zhen Yang Cui
Soo Jung Park
Eunbi Jo
In-Hu Hwang
Kyung-Bok Lee
Sung-Woo Kim
Dae Joon Kim, The University of Texas Rio Grande ValleyFollow
Jong Chun Joo
Seok Hoon Hong
Min-Goo Lee
Ik-Soon Jang

Document Type

Article

Publication Date

5-23-2018

Abstract

The chemokine, CCL5, is a key mediator for the recruitment of immune cells into tumors and tissues. Akt/NF-κB signaling is significantly activated by CCL5. However, the role of NF-κB inactivation in apoptosis induced by negative regulation of CCL5 remains unclear. Here, we analyzed the effect of cordycepin on NF-κB activity in SKOV-3 cells and found that cordycepin-mediated inhibition of NF-κB signaling induced apoptosis in SKOV-3 cells via the serial activation of caspases. In addition, immune-blotting analysis showed that CCL5 is highly expressed in SKOV-3 cells. In addition to activating caspases, we show that, cordycepin prevents TNF-α-induced increase in CCL5, Akt, NF-κB, and c-FLIPL activation and that CCL5 siRNA could inhibit Akt/NF-κB signaling. Moreover, cordycepin negatively regulated the TNF-α-mediated IκB/NF-κB pathway and c-FLIPL activation to promote JNK phosphorylation, resulting in caspase-3 activation and apoptosis. Also, we show that c-FLIPL is rapidly lost in NF-κB activation-deficient. siRNA mediated c-FLIP inhibition increased JNK. SP600125, a selective JNK inhibitor, downregulated p-JNK expression in cordycepin-treated SKOV-3 cells, leading to suppression of cordycepin-induced apoptosis. Thus, these results indicate that cordycepin inhibits CCL5-mediated Akt/NF-κB signaling, which upregulates caspase-3 activation in SKOV-3 cells, supporting the potential of cordycepin as a therapeutic agent for ovarian cancer.

Comments

Copyright © The Author(s) 2018

Recommended Citation

Cui, Z. Y., Park, S. J., Jo, E., Hwang, I. H., Lee, K. B., Kim, S. W., ... & Jang, I. S. (2018). Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-κB signaling pathway. Cell death discovery, 4(1), 62. https://doi.org/10.1038/s41420-018-0063-4

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Cell Death Discovery

DOI

10.1038/s41420-018-0063-4

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology