Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9.

Abstract

Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin.

• Authors: Chenglin Li, Dan Yang, Yuanwei Zhao, Yu Qiu, Xin Cao, Yanyan Yu, Hao Guo, Xiaoke Gu, Xiaoxing Yin
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 67 Issue 7 Pg. 1191-200 ( 2015) ISSN: 1532-7914 [Electronic] United States
• PMID: 26359917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Matrix Metalloproteinase Inhibitors
• STAT3 Transcription Factor
• STAT3 protein, human
• 3-methylquercetin
• Quercetin
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor (drug effects)
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Female
• Humans
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Matrix Metalloproteinase Inhibitors (pharmacology)
• Quercetin (analogs & derivatives, pharmacology)
• STAT3 Transcription Factor (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)