Xanthoceraside, a
saponin extracted from the husks of Xanthoceras sorbifolia Bunge, suppresses
inflammation and oxidative stress. However, the antitumor properties of
xanthoceraside as well as its mechanism of action remain unclear. Therefore, we proposed to investigate its potential anticancer property. In this study, the viability of cells was measured by the MTT assay. Cell cycle and mitochondrial membrane potential were measured by flow cytometry, and the expressions of
procaspase-9,
procaspase-3, Cyto.c, Apaf-1, Bcl-2, Bcl-xL, Bad, p53, and IGF-1R/Raf/
MEK/ERK were tested by Western blotting.
Xanthoceraside significantly inhibited the proliferation of human
melanoma A375.S2 cells in a concentration- and time-dependent manner but did not impair the viability of normal cells (peripheral blood mononuclear cells). Further analysis revealed that
xanthoceraside induced apoptosis by activating
caspase-3 and
caspase-9 in a time-dependent manner through the mitochondrial pathway but did not activate
caspase-8 in the cells. In addition,
xanthoceraside inhibited the expression of the
insulin-like growth factor-1 receptor (IGF-1R), which is an important prosurvival, antiapoptotic signaling
growth factor receptor that is frequently overexpressed in
cancer cells and used as a therapeutic target for multiple
cancers. Interestingly,
xanthoceraside also decreased the expression of Raf, p-
MEK, and p-ERK, the downstream effectors of IGF-1R. Taken together, these findings indicate that
xanthoceraside induces apoptosis through a mitochondria-mediated apoptotic pathway, which is induced by the downregulation of IGF-1R/Raf/
MEK/ERK cascades in A375.S2 cells.