Abstract— Amino acid contents of glutamic acid leucine in red ginseng marc (RGM) were higher than in ginseng body and root, Red ginseng, but the amount of arginine in RGM contains high amount of fiber and polysaccharides. This study examined whether or not methanolic extract of red ginseng marc (RGME) induces apoptosis in the human oral squamous cell carcinoma (HSC-3) along with the possible mechanism (s) of the RGME-mediated cytotoxicity. Cytotoxicity and apoptosis induction of HSC-3 cells were evidenced by MTT assay, cell morphology alteration, apoptosis enzyme-linked immunosorbent assay, flow cytometric analysis, caspase-3 activity, and protein expression by Western blotting after RGME treatment for 24 h. The RGME induced the cell death of HSC-3 cells via apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of condensed and/or fragmented nuclei, and the generation of a cleaved PARP product and characterized by activation of caspase-3. The efficacious induction of apoptosis was observed as a dose-dependent manner. The treatment of the cells with the RGME also induced changes in the mitochondrial level of the Bcl-2 family proteins such as Bcl-2 and Bax. Furthermore, the RGME increased the phosphorylation of ERK, and phospho-p38 MAPK at the same concentrations. The RGME inhibited the nuclear translocation of NF-κB by suppressing the degradation of IκB-α. Our findings clearly demonstrate that RGME induces G1 arrest, activates the MAPKs, inhibits NF-κB, and induces apoptosis of HSC-3 cells. These results strongly suggest that red ginseng marc might have cancer inhibition and therapeutic potential.
Keywords— Apoptosis, Mitochondrial pathway, Caspases, MAPKs signal pathway, Cell cycles, NF-κB, Red ginseng marc