Zingerone suppresses angiogenesisviainhibition of matrix metalloproteinases during tumor development

// Woom-Yee Bae 1, * , Jae-Sun Choi 1, * , Ja-Eun Kim 2, 3 , Chan Park 1, 2 , Joo-Won Jeong 1, 2 1 Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea 2 Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea 3 Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea * These authors contributed equally to this work Correspondence to: Joo-Won Jeong, email: jjeong@khu.ac.kr Keywords: zingerone, angiogenesis, cancer, matrix metalloproteinases, JNK Received: April 25, 2016 Accepted: June 04, 2016 Published: June 14, 2016 ABSTRACT Angiogenesis is an essential step for tumor survival and progression, and the inhibition of angiogenesis is a good strategy for tumor therapeutics. In this study, we investigated the therapeutic effect of zingerone in a mouse tumor model. Zingerone suppressed tumor progression and tumor angiogenesis. Moreover, we found that zingerone inhibited the angiogenic activities of endothelial cells by both direct and indirect means. A mechanistic study showed that the activities of MMP-2 and MMP-9 in tumor cells were decreased by treatment with zingerone. Interestingly, zingerone-mediated inhibition of MMP-2 and MMP-9 was involved in the JNK pathway. In conclusion, zingerone showed strong anti-angiogenic activity via the inhibition of MMP-2 and MMP-9 during tumor progression, suggesting that zingerone may be a potential therapeutic drug for human cancers.