Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development.
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.
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Woom-Yee
WY
Bae
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Jae-Sun
JS
Choi
Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.|Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Ja-Eun
JE
Kim
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.|Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Chan
C
Park
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.|Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Joo-Won
JW
Jeong
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D004195:Disease Models, Animal; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000201:enzymology
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D061965:Matrix Metalloproteinase Inhibitors; C013738:zingerone; D006139:Guaiacol; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
JNK; angiogenesis; cancer; matrix metalloproteinases; zingerone