Fermented So-Cheong-Ryong-Tang (FCY) induces apoptosis via the activation of caspases and the regulation of MAPK signaling pathways in cancer cells

Nam-Hui Yim, Aeyung Kim, Young Pil Jung, Taesoo Kim, Choong Je Ma, Jin Yeul Ma

So-Cheong-Ryong-Tang (CY), a traditional herbal formula, mainly has been shown to possess allergic rhinitis and asthma for hundreds of years in Asian countries. Although this medicine has been attracted Asian scientists with investigating mechanisms of action against inflammatory-related diseases, there is a little available information on the anti-cancer effect of CY, especially on the fermented form (FCY). In this study, we explored the chemopreventive/chemotherapeutic efficacy of FCY against cancer cells and proved the efficacy of FCY through performing in vivo xenograft assay. CY was fermented with bacteria and lyophilized. For analysis of the constituents of CY and FCY, high performance liquid chromatography (HPLC)-DAD system was performed. To detect the anti-cancer effect of FCY, cell viability assay, caspase activity assay, cell cycle analysis, and Western blot analysis were performed in AGS human gastric cancer cells. The inhibitory effects of tumor growth by CY and FCY were evaluated in athymic nude mice inoculated with HCT116 human colon cancer cells. As a result of analyzing the 11components present in CY and FCY, the contents of ephedrine HCl, glycyrrhizin, gingerol, schisandrin, and gomisin A were respectively increased by fermentation in FCY. The treatment of CY or FCY inhibited the viability of AGS cells, interestingly, the inhibition of cancer cell growth was enhanced by fermentation of CY. FCY induced the apoptosis through activating the caspase-3, -8, and -9. Additionally, FCY regulated the activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK). In vivo xenografts, administration of FCY significantly inhibited the tumor formation, and improved the anti-tumor effect compared to that of CY in athymic nude mice. FCY indicated significant anti-cancer effects, and its efficacy against tumor formation was improved than that of CY, therefore, FCY might be used for applications of traditional medicine against cancer in modern complementary and alternative therapeutics. Graphical Abstract ᅟ.