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

Cell Death Discovery
Zhen Yang CuiIk-Soon Jang

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 result...Continue Reading

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Citations

Feb 28, 2020·The Journal of Pharmacology and Experimental Therapeutics·Tesi LiuXiangshan Ren
Nov 27, 2019·Cancers·Mudra BinjuYu Yu
May 14, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Fu XiaomengYuan Dandan
Jul 8, 2020·Cancers·Donatella AldinucciNaike Casagrande
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Methods Mentioned

BETA
light microscopy
nuclear translocation
transfection
chip
electrophoresis

Software Mentioned

Ingenuity Pathways
DAVID
GraphPad Prism
HistoQuest
TissueGnostics
SAM
Image J

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