Abstract
This study is the first report that investigated the apoptosis-inducing effects of Cordyceps militaris (CM) and its mycelial fermentation in human glioblastoma cells. Both fractions arrested the GBM8401 cells in the G0/G1 phase, whereas the U-87MG cells were arrested at the G2/M transitional stage. Western blot data suggested that upregulation of p53 and p21 might be involved in the disruption of cell cycle progression. Induction of chromosomal condensation and the appearance of a sub-G1 hypodipoid population further supported the proapoptogenicity, possibly through the activation of caspase-3 and caspase-8, and the downregulation of antiapoptotic Bcl-2 and the upregulation of proapoptotic Bax protein expression. Downregulation of mammalian target of rapamycin and upregulation of Atg5 and LC3 II levels in GBM8401 cells implicated the involvement of autophagy. The signaling profiles with mycelial fermentation treatment indicated that mycelial fermentation triggered rapid phosphorylation of Akt, p38 MAPK, and JNK, but suppressed constitutively high levels of ERK1/2 in GBM8401 cells. Mycelial fermentation treatment only significantly increased p38 MAPK phosphorylation, but decreased constitutively high levels of Akt, ERK1/2, and JNK phosphorylation in U-87MG cells. Pretreatment with PI3K inhibitor wortmannin and MEK1 inhibitor PD98059 prevented the mycelial fermentation-induced cytotoxicity in GBM8401 and U-87MG cells, suggesting the involvement of PI3K/Akt and MEK1 pathways in mycelial fermentation-driven glioblastoma cell apoptosis and autophagy.
Highlights
Mycelial extracts, purified nature product, submerged culture, and water extract of Cordyceps have shown a number of far-reaching medicinal effects.[11]
To test the cytostatic effect of Cordyceps militaris (CM) and mycelial fermentation on the proliferation of 3T3, MCF-7, GBM8401, and U-87MG cells, the cells were treated with different concentrations of CM or mycelial fermentation
The results show that treatment with CM or mycelial fermentation significantly reduced viability of four cell lines in a dose-dependent manner (Figure 1)
Summary
Mycelial extracts, purified nature product, submerged culture, and water extract of Cordyceps have shown a number of far-reaching medicinal effects.[11] For example, mycelial extracts of Cordyceps have been found to possess diverse biological activities, including anti-inflammation, antioxidation bioactivities, and an immunostimulatory effect.[12,13,14]. Nature product of Cordyceps has shown that cordycepin, one of the main constituents of CM, exhibits an antitumor effect in some tumor cell lines.[15] Polysaccharides–peptide complexes isolated from submerged culture of C. sphecocephala mycelia induce apoptosis of human hepatocarcinoma HepG2 and neuroblastoma SKN-SH cells.[16] In addition, water extract of CM may inhibit tumor cell proliferation via arresting the cell cycle at the G2/M phase and induce apoptosis through upregulation of p53, p21, and cyclin B1, as well as the activation of caspase-8, caspase-9, and caspase-3.17,18.
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