Cordyceps militaris extract inhibits the NF-κB pathway and induces apoptosis through MKK7-JNK signaling activation in TK-10 human renal cell carcinoma

Soo Jung Park, Hyun Jin Jang, In Hu Hwang, Jung Min Kim, Eunbi Jo, Min-Goo Lee, Ik Soon Jang, Jong Cheon Joo

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)465-470
Number of pages6
JournalNatural Product Communications
Volume13
Issue number4
Publication statusPublished - 2018 Jan 1

Fingerprint

Cordyceps militaris
Cordyceps
kidney cells
Renal Cell Carcinoma
carcinoma
apoptosis
Apoptosis
extracts
small interfering RNA
Small Interfering RNA
phosphorylation
Down-Regulation
Phosphorylation
MAP Kinase Signaling System
tumor necrosis factors
drug resistance
caspase-3
Drug Resistance
Caspase 3
Transcription Factors

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 journalArticle

Park, Soo Jung ; Jang, Hyun Jin ; Hwang, In Hu ; Kim, Jung Min ; Jo, Eunbi ; Lee, Min-Goo ; Jang, Ik Soon ; Joo, Jong Cheon. / Cordyceps militaris extract inhibits the NF-κB pathway and induces apoptosis through MKK7-JNK signaling activation in TK-10 human renal cell carcinoma. In: Natural Product Communications. 2018 ; Vol. 13, No. 4. pp. 465-470.
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