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Cited 31 time in webofscience Cited 33 time in scopus
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Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-kappa B signaling pathway

Authors
Cui, Zhen YangPark, Soo JungJo, EunbiHwang, In-HuLee, Kyung-BokKim, Sung-WooKim, Dae JoonJoo, Jong ChunHong, Seok HoonLee, Min-GooJang, Ik-Soon
Issue Date
23-May-2018
Publisher
NATURE PUBLISHING GROUP
Citation
CELL DEATH DISCOVERY, v.4
Indexed
SCOPUS
Journal Title
CELL DEATH DISCOVERY
Volume
4
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/3530
DOI
10.1038/s41420-018-0063-4
ISSN
2058-7716
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.
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