Pomolic Acid Inhibits Invasion of Breast Cancer Cells Through the Suppression of CXC Chemokine Receptor Type 4 Expression.
High mortality of cancer-mediated deaths is due to metastasis. CXC chemokine receptor type 4 (CXCR4) signaling has been demonstrated to be involved in migration of breast cancer. Thus, identification of CXCR4 inhibitor has been challenged constantly as an anticancer drug. This study is aimed to investigate the CXCR4 inhibitor that could inhibit tumor metastasis from natural products. We demonstrated that pomolic acid (PA), a component of Euscaphis japonica, could downregulate CXCR4 expression in breast cancer cells. Treatment with proteasomal and lysosomal inhibitors did not show significant effects on PA's ability. When we further explored the molecular mechanism, suppression of CXCR4 occurred at transcriptional level and was correlated with inhibition of nuclear factor-kappaB (NF-κB) activation. Downregulation of CXCR4 by PA was accompanied by the inhibition of CXC motif chemokine 12 (CXCL12)-induced invasion of breast cancer cells. Overall, our results indicate that PA, as a novel inhibitor of CXCR4, can be a promising therapeutic agent for treatment of cancer metastasis.
College of Pharmacy, Keimyung University, Daegu, Republic of Korea.
Buyun
B
Kim
Department of Biotechnology, Research Institute (RIBHS) and College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk, Korea.
Ji-Hun
JH
Kim
College of Pharmacy, Keimyung University, Daegu, Republic of Korea.
Byoungduck
B
Park
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; C115535:pomolic acid; D009828:Oleanolic Acid
BREAST CANCER; CXCR4; METASTASIS