A fraction of methylene chloride from Geum japonicum Thunberg inhibits tumor metastatic and angiogenic potential.
The plant Geum japonicum Thunberg (GjT) has been used as a diuretic in traditional medicine. Herein, we report that the GjT extract blocks both the spread of human umbilical vein endothelial cells (HUVECs) on matrigel and the migration of B16 cells. We used various assays to test for cell attachment, spreading, wound healing and angiogenesis. A reverse transcription-polymerase chain reaction (RT-PCR) and a mitogen-activated protein kinase (MAPK) assay were also carried out for the mechanistic study of GjT. Our results showed that a fraction of methylene chloride fraction from GjT inhibited B16 cells during cell attachment and migration and suppressed tube formation in a dose-dependent manner. An RT-PCR analysis showed that the methylene chloride extract decreased the mRNA expression of CD44 and TIMP-2. A Western blot analysis of the phosphorylation of MAPK kinases (ERK, JNK and p38) showed that the GjT fraction increased the expression of phospho-JNK, suggesting that GjT has the potential to alleviate metastatic and angiogenic activity, via a phospho-JNK signaling pathway.
Heo
Jin-Chul
JC
Food and Bio-Industry Research Institute, Graduate School, Kyungpook National University, Daegu, Korea.
Son
Minsik
M
Woo
Sang-Uk
SU
Kweon
Mi-Ae
MA
Yoon
Eun Kyung
EK
Lee
Hee Kyung
HK
Choi
Won-Sik
WS
Cho
Kang-Jin
KJ
Lee
Sang-Han
SH
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D031986:Geum / Q000737:chemistry*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008752:Methylene Chloride / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008752:Methylene Chloride; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases