Sanguiin H6 suppresses TGF-β induction of the epithelial-mesenchymal transition and inhibits migration and invasion in A549 lung cancer.
In the epithelial-mesenchymal transition (EMT), an important cellular process, epithelial cells become mesenchymal cells. This process is also critically involved in cancer metastasis. Sanguiin H6 is a compound derived from ellagitannin, which is found in berries. Sanguiin H6 shows various pharmacological properties, including anti-angiogenic activity. Because the possible role of sanguiin H6 in the EMT and the underlying molecular mechanisms are unclear, we investigated the effect of sanguiin H6 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT and promotes lung adenocarcinoma migration and invasion through the Smad2/3 signaling pathway. Thus, to understand the inhibitory effects of sanguiin H6 on lung cancer migration and invasion, we investigated the ability of sanguiin H6 to inhibit TGF-β1-induced EMT in the A549 cell line. We found that sanguiin H6 significantly prevented the activation of Smad2/3 signaling pathway by TGF-β1. Additionally, sanguiin H6 increased the expression of the epithelial marker E-cadherin and repressed the expression of Snail and the mesenchymal marker N-cadherin during TGF-β1-induced EMT. Moreover, sanguiin H6 regulated the expression of EMT-dependent genes induced by TGF-β1. Finally, sanguiin H6 inhibited the migration and invasion of TGF-β1-stimulated A549 cells. Taken together, our findings provide new evidence that sanguiin H6 suppresses lung cancer migration and invasion in vitro by inhibiting TGF-β1 induction of the EMT.
Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
Hyeonseok
H
Ko
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, South Korea.
Hyelin
H
Jeon
College of Korean Medicine, Gachon University, Seongnam, South Korea.
Dahae
D
Lee
Division of Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do, South Korea.
Hyo-Kyoung
HK
Choi
College of Korean Medicine, Gachon University, Seongnam, South Korea. Electronic address: kkang@gachon.ac.kr.
Ki Sung
KS
Kang
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: choikc75@amc.seoul.kr.
Kyung-Chul
KC
Choi
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000970:Antineoplastic Agents; D047348:Hydrolyzable Tannins; D053773:Transforming Growth Factor beta1; C081844:sanguiin H 6
Epithelial–mesenchymal transition (EMT); Invasion; Lung cancer; Migration; Sanguiin H6; Smad2/3 signaling pathway; Transforming growth factor-beta 1 (TGF-β1)