Genomics

Dataset Information

0

Cordyceps promotes MKK7-JNK signaling pathway by reducing NF-κB/GADD45b signaling activation to induce apoptosis in TK-10 renal cell carcinoma


ABSTRACT: Cordyceps participates in various pharmacological activities including anti-tumor, and is involved in the regulation of NF-κB signaling pathway. However, the detailed role of cordycepin in suppression of NF-κB signaling pathway is less clear. In this study, we first analyzed the effect of cordyceps on NF-κB activity in TK-10 cells, and found that cordyceps resulted in a dose-dependent reduction in TNF-α-induced NF-κB activation. Here, we show that cordyceps mediated NF-kB inhibition induces apoptosis in TK-10 cells involved the serial activation of caspases. Moreover, we demonstrate that in addition to activating caspases, the cordyceps negatively modulates TNF-α-mediated NF-κB signaling to promote JNK activation, which results in apoptosis, and that NF-kB regulates antiapoptotic factor GADD45b and the JNK kinase MKK7. When the TNFα cytokine binds to the TNF receptor, IκB dissociates from NF-κB. As a result, the active NF-κB translocates to the nucleus. Cordyceps clearly prevented NF-κB from mobilizing to the nucleus, resulting in downregulation of GADD45b, whereas upregulation of MKK7 and phosphorylation of JNK (p-JNK). This increased Bax activation, leading to marked cordyceps-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Furthermore, siRNA mediated inhibition of MKK7 downregulated p-JNK and The JNK inhibitor SP600125 strongly inhibited Bax. Thus, these results indicate that cordyceps inhibits NF-κB/GADD45b signaling activation to upregulate MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells and support the potential of cordyceps as a therapeutic agent for renal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81728 | GEO | 2016/05/24

SECONDARY ACCESSION(S): PRJNA322443

REPOSITORIES: GEO

Similar Datasets

| PRJNA322443 | ENA
2016-05-24 | GSE81727 | GEO
| E-GEOD-6559 | biostudies-arrayexpress
2007-01-02 | GSE6559 | GEO
| E-GEOD-2190 | biostudies-arrayexpress
2005-11-09 | GSE2190 | GEO
2016-09-17 | GSE87024 | GEO
2016-09-17 | GSE87023 | GEO
2018-01-22 | GSE65193 | GEO
| E-GEOD-31258 | biostudies-arrayexpress