Pomolic acid inhibits metastasis of HER2 overexpressing breast cancer cells through inactivation of the ERK pathway

Abstract

Expression of the CXC chemokine receptor-4 (CXCR4), a G protein-coupled receptor, and HER2, a receptor tyrosine kinase, strongly correlates with tumor progression and metastatic potential of breast cancer cells. We report the identification of pomolic acid (PA) as a novel regulator of HER2 and CXCR4 expression. We found that PA downregulated the expression of HER2 and CXCR4 in SKBR3 cells in a dose- and time-dependent manner. When investigated for the molecular mechanism(s), it was found that the downregulation of HER2 and CXCR4 was not due to proteolytic degradation but rather to transcriptional regulation as indicated by downregulation of mRNA expression. Moreover, we show that PA inhibits phosphorylation of ERK and reduces NF-κB activation. Suppression of CXCR4 expression by PA correlated with the inhibition of CXCL12-induced invasion of HER2-overexpressing breast cancer cells. Overall, our results demonstrate for the first time that PA is a novel inhibitor of HER2 and CXCR4 expression via kinase pathways and may play a critical role in determining the metastatic potential of breast cancer cells.

Molecular genomic features associated with in vitro response of the NCI‐60 cancer cell line panel to natural products

“…Pomolic acid, an active triterpene from Euscaphis japonica and Salvia officinalis (sage), has strong antitumor and antiproliferative properties. It inhibits tumor cell growth, promotes apoptosis and can interact with or downregulate components of multiple cancer pathways [23,94,95]. Earlier studies of the NCI-60 dataset suggested inhibition of the pathways in which EGF and EGFR are involved by pomolic acid [23].…”

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

“…Increasing evidence demonstrated that pomolic acid exerts anti-cancer activity by inducing apoptotic cell death and inhibiting invasion and metastasis [ 222 , 223 , 224 ]. Pomolic acid also mitigates multidrug resistance via inhibiting ABCB1 activity [ 225 ].…”