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 journalArticlepeer-review

    4 Citations (Scopus)

    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
    DOIs
    Publication statusPublished - 2018 Apr

    Keywords

    • Apoptosis
    • Cordyceps militaris
    • JNK
    • MKK7
    • NF-κB
    • TK-10.

    ASJC Scopus subject areas

    • Pharmacology
    • Plant Science
    • Drug Discovery
    • Complementary and alternative medicine

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