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.

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of Pharbitis nil, also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether Pharbitis nil seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Seeds of Pharbitis nil (Pharbitis semen) were separated by chromatography and the active compound of Pharbitis semen (PN) was purified by HPLC. The compound PN efficiently suppressed the proliferation of mutated KRAS-driven CRC cells and their clonogenic potentials in a concentration-dependent manner. It also induced apoptosis of SW480 human colon cancer cells and cell cycle arrest at the G2/M phase. The CRC related pathways, including RAS/ERK and AKT/mTOR, were assessed and PN reduced the phosphorylation of AKT and mTOR. Furthermore, PN preserved muscle cell proliferation and myotube formation in cancer conditioned media. In summary, PN significantly suppressed mutated KRAS-driven cell growth and reserved muscle cell function. Based on the current study, PN could be considered as a promising starting point for the development of a nature-derived drug against KRAS-mutated CRC progression.