Involvement of p38 MAPK in the Anticancer Activity of Cultivated Cordyceps militaris

Abstract

Cordyceps militaris is a traditional Chinese medicine frequently used for tonic and therapeutic purposes. Reports from our laboratory and others have demonstrated that extracts of the cultivated fruiting bodies of C. militaris (CM) exhibit a potent cytotoxic effect against many cancer cell lines, especially human leukemia cells. Here, we further investigated the underlying mechanism through which CM is cytotoxic to cancer cells. The CM-mediated induction of PARP cleavage and its related DNA damage signal (γH2AX) was diminished by caspase inhibitor I. In contrast, a ROS scavenger failed to prevent CM-mediated leukemia cell death. Moreover, two signaling molecules, AKT and p38 MAPK, were activated during the course of apoptosis induction. Employing MTT analysis, we found that a p38 MAPK inhibitor but not an AKT inhibitor could rescue cells from CM-mediated cell death, as well as inhibit the cleavage of PARP, formation of apoptotic bodies and up-regulation of the γH2AX signal. These results suggest that CM-mediated leukemia cell death occurs through the activation of the p38 MAPK pathway, indicating its potential therapeutic effects against human leukemia.

Immunostimulatory effects of cordycepin‐enriched WIB‐801CE from Cordyceps militaris in splenocytes and cyclophosphamide‐induced immunosuppressed mice

“…C . militaris exhibits anticancer, antioxidant, antiinflammatory, antihyperglycemic, and antimetastatic effects (Chou, Lai, Hong, et al, ; Huang, Lin, Mau, et al, ; S. Liu, Tang, Huang, et al, ). The immunomodulating activities of C .…”

“…Liu, Kopparapu, Li, et al, 2017). Abbreviations: Con A, concanavalin A; IFN-γ, interferon-γ; IL, interleukin; MTX, methotrexate; NK, natural killer; TNF-α, tumor necrosis factor-α C. militaris exhibits anticancer, antioxidant, antiinflammatory, antihyperglycemic, and antimetastatic effects (Chou, Lai, Hong, et al, 2015;Huang, Lin, Mau, et al, 2015;S. Liu, Tang, Huang, et al, 2015).…”

Cistanche Tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect Through Combination With Cisplatin

“…The activation of p38 and JNK can induce apoptosis but the activation of ERK1/2 can be an anti-apoptotic or pro-apoptotic agent depending on the cell properties [33]. It has been reported that CHM induced the apoptosis of tumor cells by activating p38, JNK or ERK MAPK pathways [34,35]. We found that CTPG up-regulated the phosphorylated levels of p38, JNK and ERK, suggesting that MAPK signaling pathway might be involved in the apoptosis of HCC cells induced by CTPG.…”

HPLC determination of massoia lactone in fermented Cordyceps sinensis mycelium Cs‐4 and its anticancer activity in vitro

“…Because of the encouraging effectiveness, few side effects and overwhelming resistance to drugs, C. sinensis has been increasingly utilized as an antitumor herb in Chinese medicine and an adjuvant of chemo‐ and radiotherapy for the treatment of cancers (Chen, Wang, Nie, & Marcone, 2013; Santos et al., 2018; Xie et al., 2018). Previous studies on the anticancer capacities of fermented C. sinensis have mainly focused on their water or organic extracts (Chou et al., 2015; Kubo et al., 2010, 2012). In contrast, the antitumor potency of the volatile oils was seldom evaluated.…”