Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2 -9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways.
Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, has been used as a folk medicine in the Chinese population for centuries and is known to have diverse pharmacologic effects, including anti-proliferative and anti-cancer actions. However, the effects of Gyp on prevention from invasion and migration of oral cancer cells are still unsatisfactory. The purpose of this study was to investigate effects of Gyp treatment on migration and invasion of SAS human oral cancer cells. SAS cells were cultured in the presence of 90 and 180 μg/mL Gyp for 24 and 48 hours. Gyp induced cytotoxic effects and inhibited SAS cells migration and invasion in dose- and time-dependent response. Wound-healing assay and boyden chamber assay were carried out to investigate Gyp-inhibited migration and invasion of SAS cells. Gyp decreased the abundance of several proteins, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/ 2), matrix metalloproteinase-9, -2 (MMP-9, -2), sevenless homolog (SOS), Ras, urokinase-type plasminogen activator (uPA), focal adhesion kinase (FAK) and RAC-alpha serine/threonine-protein kinase (Akt), in a time-dependent manner. In addition, Gyp decreased mRNA levels of MMP-2, MMP-7, MMP-9 but did not affect FAK and Rho A mRNA levels in SAS cells. These results provide evidences for the role of Gyp as a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of oral cancer cells. The inhibition of NF-κB and MMP-2, -7 and -9 signaling may be one of the mechanisms that is present in Gyp-inhibited cancer cell invasion and migration.
Lu
Kung-Wen
KW
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Chen
Jung-Chou
JC
Lai
Tung-Yuan
TY
Yang
Jai-Sing
JS
Weng
Shu-Wen
SW
Ma
Yi-Shih
YS
Lu
Pei-Jung
PJ
Weng
Jing-Ru
JR
Chueh
Fu-Shin
FS
Wood
W Gibson
WG
Chung
Jing-Gung
JG
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D029774:Gynostemma; D006801:Humans; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; C474918:gypenoside; D048049:Extracellular Signal-Regulated MAP Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2