Cordyceps militaris Extract Inhibits the NF-κB pathway and Induces Apoptosis through MKK7-JNK Signaling Activation in TK-10 Human Renal Cell Carcinoma

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 siRNAmediated 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.

Cordyceps militaris Exerts Anticancer Effect on Non–Small Cell Lung Cancer by Inhibiting Hedgehog Signaling via Suppression of TCTN3

“…In addition, apoptosis was induced in human ovarian cancer and renal carcinoma in vitro and in vivo by C militaris , which was related to cordycepin. 42,43 Currently, C militaris has received considerable attention worldwide as a potential source of anticancer drugs. 44 However, the molecular mechanism underlying the C militaris –induced inhibition of tumor cell growth and apoptosis remains unclear.…”

Cordyceps militaris Exerts Antitumor Effect on Carboplatin-Resistant Ovarian Cancer via Activation of ATF3/TP53 Signaling In Vitro and In Vivo

“…The quality evaluation of CME, as determined using a high-resolution mass spectrometer, a traditional medicine library, and the nucleotide and cordycepin quadrupole time-offlight (Q-TOF) mass spectrometry analysis was shown in our previous study. 37…”

Changes in Functionality of Tenebrio molitor Larvae Fermented by Cordyceps militaris Mycelia

“…Cordyceps militaris , called Dong-Chong-Xia-Cao, which includes means of winter worm transforming into summer grass, is one of the entomogenous fungi that form a fruiting body mainly on pupae or larvae [ 12 , 13 ]. It has been traditionally used as an herbal medicine in Korea and China to enhance longevity and vitality [ 14 ] and contains many types of biologically active compounds such as cordycepin, adenosine, cordycepic acid, sterols, nucleosides, and polysaccharides [ 15 ]. Among them, cordycepin (3′-deoxyadenosine), a derivative of adenosine, was the first compound to be isolated from C. militaris [ 16 ].…”