Baohuoside I suppresses invasion of cervical and breast cancer cells through the downregulation of CXCR4 chemokine receptor expression.

Abstract

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.

• Authors: Buyun Kim, Byoungduck Park
• Journal: Biochemistry (Biochemistry) Vol. 53 Issue 48 Pg. 7562-9 (Dec 09 2014) ISSN: 1520-4995 [Electronic] United States
• PMID: 25407882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• CXCR4 protein, human
• Flavonoids
• RNA, Messenger
• RNA, Neoplasm
• Receptors, CXCR4
• baohuoside I

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Epimedium
• Female
• Flavonoids (administration & dosage, pharmacology)
• HeLa Cells
• Hep G2 Cells
• Humans
• Neoplasm Invasiveness (prevention & control)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Receptors, CXCR4 (antagonists & inhibitors, genetics)
• Uterine Cervical Neoplasms (drug therapy, genetics, pathology)