Isoorientin Suppresses Invasion of Breast and Colon Cancer Cells by Inhibition of CXC Chemokine Receptor 4 Expression

Abstract

Cancer metastasis still accounts for up to 90% of cancer-related deaths, but the molecular mechanism for metastasis is unclear. Several chemokines and their receptors mediate tumor cell metastasis, particularly through long-term effects that regulate angiogenesis, tumor cell proliferation and apoptosis. Among them, CXC chemokine receptor 4 (CXCR4) has been shown to play a pivotal role in cancer metastasis through interaction with a ligand (CXCL12), also known as stromal cell-derived factor 1α (SDF-1α). The CXCR4 promoter region is well characterized, and its expression is controlled by various transcriptional factors, including NF-κB, HIF−1α, and so forth. Isoorientin (ISO) is a 3', 4', 5, 7-tetrahydroxy-6-C-glucopyranosyl flavone. ISO has been reported to exhibit anti-oxidant, anti-cancer, and anti-inflammatory properties. However, the anti-metastatic effect of ISO following downregulation of CXCR4 is unknown, and the mechanism underlying the antitumor activity has yet to be elucidated. In our present study, we showed that ISO inhibited the expression of CXCR4 through NF-κB regulation in breast and colon cancer cells. We have also demonstrated that ISO inhibits CXCR4 expression in a variety of tumor cells. Furthermore, we found that CXCR4 expression is regulated through inhibition of the transcription process. Inhibition of CXCR4 expression also reduced the invasion of cancer cells by CXCL12. In conclusion, our results suggest that ISO is a novel inhibitor to regulate CXCR4 expression and the key molecule contributing to antitumor activity.