Cordyceps militaris Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway

Abstract

Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer which is notorious for its un-druggable features and the ineffectiveness of conventional therapies against it. GSC extract was prepared and its proximate composition and amino acids were analyzed. The suppressive effects were investigated with the KRAS-driven colorectal cancer cell-line, SW480. SW480 proliferation, clonogenic potential, apoptosis, and the RAS/extracellular signal-regulated kinase (ERK) pathway under the GSC treatment were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot, respectively. An in vivo experiment with the SW480 xenograft mouse model was performed. As a result, GSC suppressed cell proliferation by inducing the apoptosis of KRAS-driven colorectal cancer cells and inhibited clonogenic capabilities. The decrease of KRAS and ERK phosphorylation was detected by Western blot. Tumor growth was significantly suppressed when GSC was introduced to the tumor-xenograft mouse model. In conclusion, GSC suppressed KRAS-driven colorectal cancer growth both in vitro and in vivo, and can be used as an alternative or simultaneous approach in colorectal cancer therapy.

Cordyceps militaris Modulates Intestinal Barrier Function and Gut Microbiota in a Pig Model

“…CM possess multi-functions of enhancing immunity, anti-inflammatory and antioxidant with fewer adverse effects, foe it’s enriched in active ingredients such as cordyceps polysaccharide, D-mannitol, and cordycepin, etc. ( Wang et al, 2012 ; Seo et al, 2018 ). Currently, artificial culture of CM has greatly increased its production and lowered its cost ( Dong et al, 2015 ; Lou et al, 2019 ).…”

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy

“…By contrast, CM had little effect on nonprostatic human endometrial epithelial cells. It is reported that Cordyceps militaris extract inhibited the proliferation of breast cancer, ovarian cancer, nonsmall-cell lung cancer, and colorectal cancer cells through androgen-independent signaling pathways [ 22 , 23 , 24 , 25 ]. Given that the CM-induced decrease in prostate hyperplasia was independent of the serum level of testosterone, CM may regulate the proliferation of prostate cells by inhibiting the activation of intracellular signal pathways other than those involved in testosterone signaling.…”

Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression

“…However, limited studies have examined the effects of natural extracts targeting mutated KRAS-driven CRC and none of these studies tested the efficacy of these extracts on muscle function. In our previous study, Cordyceps militaris germinated soybeans suppressed mutated KRAS-driven CRC via the RAS/ERK pathway [14]. Phellinus linteus grown on germinated brown rice increased the sensitivity of Cetuximab to inhibit KRAS-CRC progression both in vitro and in vivo [15].…”

“…Western blot analysis was performed in triplicate as previously described [14]. Cells were treated with compound PN (0.5-4 µg/mL) for 48 h and detached with trypsin-EDTA.…”