More than 90 percent of
cancer-mediated deaths are due to
metastasis, but the mechanisms that control
metastasis remain poorly understood. Thus, the
therapy targeting this process has been challenged constantly, but no
therapy has yet been approved.
CXC chemokine receptor 4 (CXCR4), a Gi
protein-coupled receptor for the
CXC chemokine ligand (CXCL) 12/stromal cell derived factor (SDF) 1α, is known to be expressed in various
tumors. Recently, the CXCL12/CXCR4 axis has emerged as a key mediator of
tumor metastasis; therefore, the possibility that identification of CXCR4 inhibitors can be a promising strategy for abrogating
metastasis has been considered. In this report, we investigate
baohuoside I, a component of Epimedium koreanum, as a regulator of CXCR4 expression as well as function in
cervical cancer and
breast cancer cells. We observed that
baohuoside I downregulated CXCR4 expression in a dose- and time-dependent manner in HeLa cells. Treatment with a pharmacological
proteasome and lysosomal inhibitors did not have a substantial effect on
baohuoside I's ability to suppress CXCR4 expression. When we investigated the molecular mechanism of action, it was observed that the suppression of CXCR4 expression occurred at the level of
mRNA. The decrease in the level of CXCR4 expression caused by
baohuoside I was correlated with inhibition of the CXCL12-induced invasion of both cervical and
breast cancer cells. Overall, our results show that
baohuoside I exerts its antimetastatic effect through the downregulation of CXCR4 expression and, thus, has the potential to play a role in the suppression of
cancer metastasis.