Abstract
The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militaris extract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.
| Original language | English |
|---|---|
| Pages (from-to) | 465-470 |
| Number of pages | 6 |
| Journal | Natural Product Communications |
| Volume | 13 |
| Issue number | 4 |
| Publication status | Published - 2018 Jan 1 |
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Keywords
- Apoptosis
- Cordyceps militaris
- JNK
- MKK7
- NF-κB
- TK-10.
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Plant Science
- Complementary and alternative medicine
Cite this
Cordyceps militaris extract inhibits the NF-κB pathway and induces apoptosis through MKK7-JNK signaling activation in TK-10 human renal cell carcinoma. / Park, Soo Jung; Jang, Hyun Jin; Hwang, In Hu; Kim, Jung Min; Jo, Eunbi; Lee, Min-Goo; Jang, Ik Soon; Joo, Jong Cheon.
In: Natural Product Communications, Vol. 13, No. 4, 01.01.2018, p. 465-470.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cordyceps militaris extract inhibits the NF-κB pathway and induces apoptosis through MKK7-JNK signaling activation in TK-10 human renal cell carcinoma
AU - Park, Soo Jung
AU - Jang, Hyun Jin
AU - Hwang, In Hu
AU - Kim, Jung Min
AU - Jo, Eunbi
AU - Lee, Min-Goo
AU - Jang, Ik Soon
AU - Joo, Jong Cheon
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militaris extract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.
AB - The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militaris extract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.
KW - Apoptosis
KW - Cordyceps militaris
KW - JNK
KW - MKK7
KW - NF-κB
KW - TK-10.
UR - http://www.scopus.com/inward/record.url?scp=85048095503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048095503&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:85048095503
VL - 13
SP - 465
EP - 470
JO - Natural Product Communications
JF - Natural Product Communications
SN - 1934-578X
IS - 4
ER -