Cell Biochemistry and Biophysics

, Volume 60, Issue 3, pp 297–310

α-Tomatine Suppresses Invasion and Migration of Human Non-Small Cell Lung Cancer NCI-H460 Cells Through Inactivating FAK/PI3K/Akt Signaling Pathway and Reducing Binding Activity of NF-κB

  • Jiunn-Min Shieh
  • Tsan-Hwang Cheng
  • Ming-Der Shi
  • Pei-Fen Wu
  • Yi Chen
  • Shian-Chin Ko
  • Yuan-Wei Shih
Original Paper

DOI: 10.1007/s12013-011-9152-1

Cite this article as:
Shieh, JM., Cheng, TH., Shi, MD. et al. Cell Biochem Biophys (2011) 60: 297. doi:10.1007/s12013-011-9152-1

Abstract

α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring steroidal glycoalkaloid in immature green tomatoes. Some reports demonstrated that α-tomatine had various anticarcinogenic properties. The purpose of this study is to investigate the anti-metastatic effect of α-tomatine in NCI-H460 human non-small cell lung cancer cells. First, the results showed that α-tomatine significantly suppressed the abilities of the adhesion, invasion, and migration of NCI-H460 cells under non-cytotoxic concentrations. Molecular data also showed α-tomatine could inhibit the activation of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signal involve in the downregulation the enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-7 (MMP-7). Next, α-tomatine also strongly inhibited the degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding ability of NF-κB by α-tomatine treatment was further observed. Furthermore, α-tomatine significantly decreased the levels of phospho-Akt and MMP-7 in Akt1-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Presented results indicated α-tomatine might be further application for treating cancer metastasis.

Keywords

α-Tomatine Invasion Migration FAK PI3K/Akt MMP-7 

Abbreviations

MMPs

Matrix metalloproteinases

ECM

Extracellular matrix

MAPK

Mitogen-activated protein kinase

ERK

Extracellular signaling-regulating kinase

JNK/SAPK

c-Jun N-terminal kinase/stress-activated protein kinase

PI3K

Phosphoinositide 3-kinase

NF-κb

Nuclear factor kappa B

AP-1

Activator protein-1

IκB

Inhibitor of NF-κB

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jiunn-Min Shieh
    • 1
    • 2
  • Tsan-Hwang Cheng
    • 3
  • Ming-Der Shi
    • 4
    • 5
  • Pei-Fen Wu
    • 6
  • Yi Chen
    • 7
    • 8
  • Shian-Chin Ko
    • 1
    • 2
  • Yuan-Wei Shih
    • 3
  1. 1.Division of Chest Medicine, Department of Internal Medicine, Chi-Mei Medical CenterYong-Kang, TainanTaiwan
  2. 2.Department of Respiratory CareChang Jung Christian University, Chang Jung Christian UniversityTainanTaiwan
  3. 3.Department of Biological Science and Technology and Graduate Institute of Biomedical ScienceChung Hwa University of Medical TechnologyTainanTaiwan
  4. 4.Department of Medical Technology, Yongkang Veterans HospitalTainanTaiwan
  5. 5.Department of Medical Laboratory and Biotechnology ScienceKaohsiung Medical UniversityKaohsiungTaiwan
  6. 6.Department of Occupational Safety and HygieneTajen UniversityPingtungTaiwan
  7. 7.Department of Surgery, Tainan Municipal HospitalTainanTaiwan
  8. 8.Department of Health Care AdministrationChung Hwa University of Medical Technology, No. 89TainanTaiwan

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