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.
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.
Division of Chest Medicine, Department of Internal Medicine, Chi-Mei Medical Center, No. 901, Jhong-Hua Road, Yong-Kang, Tainan 710, Taiwan.
Jiunn-Min
JM
Shieh
Tsan-Hwang
TH
Cheng
Ming-Der
MD
Shi
Pei-Fen
PF
Wu
Yi
Y
Chen
Shian-Chin
SC
Ko
Yuan-Wei
YW
Shih
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018551:Solanum lycopersicum / Q000737:chemistry; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014053:Tomatine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C484751:alpha-tomatine; D014053:Tomatine; D058539:Phosphatidylinositol 3-Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020783:Matrix Metalloproteinase 7