Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA/MMP Expression through the FAK to ERK Pathways

Hsing-Chen Wu¹, Chi-Ting Horng^2,3*, You-Li Lee⁴, Pei-Ni Chen^3,5, Chin-Yin Lin³, Chen-Yu Liao³, Yih-Shou Hsieh^3,5✉, Shu-Chen Chu^6✉

1. Department of Nutrition, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan, ROC;
2. Departmant of Ophthalmology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan;
3. Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University, Taichung City, Taiwan;
4. Department of Nutrition, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan, ROC;
5. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan;
6. Institute and Department of Food Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
* Chi-Ting Horng contributed equally as first author.

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Citation:
Wu HC, Horng CT, Lee YL, Chen PN, Lin CY, Liao CY, Hsieh YS, Chu SC. Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA/MMP Expression through the FAK to ERK Pathways. Int J Med Sci 2018; 15(2):115-123. doi:10.7150/ijms.22293. Available from http://www.medsci.org/v15p0115.htm

Abstract

Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate future clinical trials of lung adenocarcinoma chemotherapy to confirm the promising results.

Keywords: FAK, ERK, metastasis, lung cancer, Cinnamomum cassia.