Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells
- Authors
- Park, Mi Kyung; Jo, Seung Ho; Lee, Hye Ja; Kang, June Hee; Kim, You Ri; Kim, Hyun Ji; Lee, Eun Ji; Koh, Jae Young; Ahn, Kyung Ok; Jung, Kyung Chae; Oh, Seung Hyun; Kim, Soo Youl; Lee, Chang Hoon
- Issue Date
- 7-Feb-2013
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Cardamonin; Transglutaminase-2; Matrix metalloproteinases; NF-kappa B; Migration; Invasion
- Citation
- LIFE SCIENCES, v.92, no.2, pp.154 - 160
- Journal Title
- LIFE SCIENCES
- Volume
- 92
- Number
- 2
- Start Page
- 154
- End Page
- 160
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14742
- DOI
- 10.1016/j.lfs.2012.11.009
- ISSN
- 0024-3205
- Abstract
- Aims: Alpinia kaisumadai was recently found in our previous study to have anti-migratory and anti-invasion activities against HT-1080 cells. However, the study did not demonstrate the exact component of Alpinia katsumadai with anti-migratory and anti-invasive activities. We tested the effects and relevant mechanism of cardamonin (CDN) on the migration and invasion of cancer cells. Main methods: Migration and invasion of cancer cells were measured using multi-well chambers. Zymography and Western blots were used to examine the effects of CDN on the activities of matrix metalloproteinases (MMPs) and expression of transglutaminase-2 (Tgase-2). Key findings: CDN, but not alpinetin, dose-dependently suppressed the migration and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion of HT-1080 sarcoma cells. CDN suppressed the expression of Tgase-2, MMP-2, NF-kappa B and MMP-9 in HT-1080 cells, and suppressed MMP-2 and MMP-9 activities. Gene silencing of Tgase-2 suppressed the migration and invasion of HT-1080 cells and suppressed the activities of MMP-2 and MMP-9. Migration of various cancer cells having high levels of Tgase-2 were also inhibited by CDN. CDN and Alpinia katsumadai extracts also directly inhibited the activity of Tgase-2. Significance: CDN inhibits migration of several cancer cell lines expressing Tgase-2 via suppression of Tgase-2 expression and inhibition of Tgase-2 activity. The finding that CON has Tgase-2 inhibitory activity will give us a new scaffold or clue of pharmacophore for the development of more effective Tgase-2 inhibitors. (C) 2012 Elsevier Inc. All rights reserved.
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