Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-kappa B signaling pathway
- Authors
- Cui, Zhen Yang; Park, Soo Jung; Jo, Eunbi; Hwang, In-Hu; Lee, Kyung-Bok; Kim, Sung-Woo; Kim, Dae Joon; Joo, Jong Chun; Hong, Seok Hoon; Lee, Min-Goo; Jang, Ik-Soon
- Issue Date
- 23-5월-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- CELL DEATH DISCOVERY, v.4
- Indexed
- SCOPUS
- Journal Title
- CELL DEATH DISCOVERY
- Volume
- 4
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/75502
- DOI
- 10.1038/s41420-018-0063-4
- ISSN
- 2058-7716
- Abstract
- The chemokine, CCL5, is a key mediator for the recruitment of immune cells into tumors and tissues. Akt/NF-kappa B signaling is significantly activated by CCL5. However, the role of NE-kappa B inactivation in apoptosis induced by negative regulation of CCL5 remains unclear. Here, we analyzed the effect of cordycepin on NE-kappa B activity in SKOV-3 cells and found that cordycepin-mediated inhibition of NE-kappa B 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 INF-alpha-induced increase in CCL5, Akt, NE-kappa B, and c-FLIPL activation and that CCL5 siRNA could inhibit Akt/NF-kappa B signaling. Moreover, cordycepin negatively regulated the INF-a-mediated IKB/NE-kappa B 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 NE-kappa B activation-deficient. siRNA mediated c-FLIP inhibition increased INK. 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-kappa B signaling, which upregulates caspase-3 activation in SKOV-3 cells, supporting the potential of cordycepin as a therapeutic agent for ovarian cancer.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.