Flavonoids from Citrus unshiu Marc. inhibit cancer cell adhesion to endothelial cells by selective inhibition of VCAM-1.

Abstract

Citrus fruits have been used as edible fruit and a component of traditional medicine for various diseases including cancer since ancient times. Herein, we investigated the anticancer activity of flavonoids of Citrus unshiu Marc. (FCM) focusing on anti-metastatic effects. We prepared FCM and performed experiments using MDA-MB-231 human breast cancer cells. FCM inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. FCM inhibited the expression of VCAM-1, but not of ICAM-1, on MDA-MB-231 cells as well as HUVECs. FCM inhibited protein kinase C (PKC) phosphorylation, but not Akt phosphorylation. FCM also inhibited cancer cell invasion in a dose-dependent manner, but not MMP-9 expression. In conclusion, this study suggested that FCM inhibits TNF-induced cancer cell adhesion to HUVECs by inhibiting VCAM-1 through inhibition of PKC, providing evidence that FCM have anti-metastatic activity by inhibiting adhesion molecules and invasion on human breast cancer cells.

• Authors: Hana Jin, Won Sup Lee, Jeong Won Yun, Ji Hyun Jung, Sang Mi Yi, Hye Jung Kim, Yung Hyun Choi, Gonsup Kim, Jin-Myung Jung, Chung Ho Ryu, Sung Chul Shin, Soon Chan Hong
• Journal: Oncology reports (Oncol Rep) Vol. 30 Issue 5 Pg. 2336-42 (Nov 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24002113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Plant Extracts
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1

Topics

• Breast Neoplasms
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Citrus (chemistry)
• Endothelial Cells (drug effects)
• Female
• Flavonoids (administration & dosage, chemistry)
• Gene Expression Regulation, Neoplastic (drug effects)
• Human Umbilical Vein Endothelial Cells
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis (drug therapy, pathology)
• Plant Extracts (administration & dosage, chemistry)
• Vascular Cell Adhesion Molecule-1 (metabolism)