Inhibitory effect of penta-acetyl geniposide on C6 glioma cells metastasis by inhibiting matrix metalloproteinase-2 expression involved in both the PI3K and ERK signaling pathways.
Penta-acetyl geniposide [(Ac)(5)GP], an acetylated geniposide product from Gardenia fructus, has been known to have hepatoprotective properties and recent studies have revealed its anti-proliferative and apoptotic effect on C6 glioma cells. In this study, we first report the anti-metastastic effect of (Ac)(5)GP in the rat neuroblastoma line: C6 glioma cells. First (Ac)(5)GP exhibited an inhibitory effect on abilities of adhesion and motility by cell-matrix adhesion assay, wound healing assay and Boyden chamber assay. Second, the decreasing activity of matrix metalloproteinase-2 (MMP-2) was noted by gelatin zymography assay. Further analysis with semi-quantitative RT-PCR showed the mRNA levels of MMP-2 and membrane type I matrix metalloproteinase (MT1-MMP) were significantly reduced, while the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) was elevated by (Ac)(5)GP treatment. Further (Ac)(5)GP also exerted an inhibitory effect on phosphoinositide 3-kinase (PI3K) protein expression, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and inhibition of activation of transcription factor nuclear factor kappa B (NF-kappaB), c-Fos, c-Jun. These findings proved (Ac)(5)GP is highly likely to be a inhibiting cancer migration agent to be further developed in the future.
Huang
Hui-Pei
HP
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110 Section 1 Chien-Kauo N. Road, Taichung, Taiwan.
Shih
Yuan-Wei
YW
Wu
Cheng-Hsun
CH
Lai
Po-Ju
PJ
Hung
Chi-Nan
CN
Wang
Chau-Jong
CJ
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005910:Glioma / Q000473:pathology*; D005960:Glucosides / Q000494:pharmacology*; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
D017931:DNA Primers; D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C074968:pentaacetyl geniposide; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases