Tags

Type your tag names separated by a space and hit enter

Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells.
Bioorg Med Chem Lett. 2017 02 15; 27(4):1081-1088.BM

Abstract

The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-β1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-β1 induced EMT. In addition, ZD 2-1 inhibited the TGF-β1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-β1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-β1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-β1 induced EMT.

Authors+Show Affiliations

Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea; Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.Natural Constituents Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.Natural Constituents Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea. Electronic address: drug9054@naver.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28110870

Citation

Kim, Young-Joo, et al. "Combined Treatment With Zingerone and Its Novel Derivative Synergistically Inhibits TGF-β1 Induced Epithelial-mesenchymal Transition, Migration and Invasion of Human Hepatocellular Carcinoma Cells." Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 4, 2017, pp. 1081-1088.
Kim YJ, Jeon Y, Kim T, et al. Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorg Med Chem Lett. 2017;27(4):1081-1088.
Kim, Y. J., Jeon, Y., Kim, T., Lim, W. C., Ham, J., Park, Y. N., Kim, T. J., & Ko, H. (2017). Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorganic & Medicinal Chemistry Letters, 27(4), 1081-1088. https://doi.org/10.1016/j.bmcl.2016.12.042
Kim YJ, et al. Combined Treatment With Zingerone and Its Novel Derivative Synergistically Inhibits TGF-β1 Induced Epithelial-mesenchymal Transition, Migration and Invasion of Human Hepatocellular Carcinoma Cells. Bioorg Med Chem Lett. 2017 02 15;27(4):1081-1088. PubMed PMID: 28110870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. AU - Kim,Young-Joo, AU - Jeon,Youngsic, AU - Kim,Taejung, AU - Lim,Won-Chul, AU - Ham,Jungyeob, AU - Park,Young Nyun, AU - Kim,Tae-Jin, AU - Ko,Hyeonseok, Y1 - 2016/12/20/ PY - 2016/10/18/received PY - 2016/12/02/revised PY - 2016/12/15/accepted PY - 2017/1/24/pubmed PY - 2017/8/19/medline PY - 2017/1/24/entrez KW - Epithelial–mesenchymal transition (EMT) KW - Hepatocellular carcinoma cancer KW - Metastasis KW - Transforming growth factor-beta 1 (TGF-β1) KW - Zingerone SP - 1081 EP - 1088 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 27 IS - 4 N2 - The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-β1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-β1 induced EMT. In addition, ZD 2-1 inhibited the TGF-β1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-β1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-β1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-β1 induced EMT. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/28110870/Combined_treatment_with_zingerone_and_its_novel_derivative_synergistically_inhibits_TGF_β1_induced_epithelial_mesenchymal_transition_migration_and_invasion_of_human_hepatocellular_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(16)31311-7 DB - PRIME DP - Unbound Medicine ER -