Anti-cancer effects of CME-1, a novel polysaccharide, purified from the mycelia of Cordyceps sinensis against B16-F10 melanoma cells.
BACKGROUND
Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In melanoma, several signaling pathways are constitutively activated. Among these, the mitogen-activated protein kinase (MAPKs) signaling pathways are activated through multiple signal transduction molecules and appear to play major roles in melanoma progression. Therefore, the inhibition of MAPK signaling might be a crucial role for the treatment of melanoma cancer.


OBJECTIVE
We examined the anticancer effect of CME-1, a novel water-soluble polysaccharide fraction, isolated from Cordyceps sinensis mycelia on B16-F10 melanoma cells.


METHODS
B16-F10 cells were exposed to different concentrations of CME-1 (250, 500 and 800 μg/ml) for 24 h in 5% CO² incubator at 37°C. Western blot analysis was performed to detect the expression of MMP-1, p-p38 MAPK, p-ERK1/2, and IkB-α in B16-F10 cells. Cell migration test was performed by wound healing migration assay.


RESULTS
CME-1 suppresses cell migration in a concentration-dependent manner. Western blotting analysis revealed that CME-1 led to the reduction on the expression levels of MMP-1 and down regulated the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2 and p38 mitogen-activated protein kinase (p38 MAPK). CME-1 restored the IkB-degradation in B16F10 cells.


CONCLUSIONS
These results indicate that CME-1 inhibited MMP-1 expressions in B16F10 melanoma cells through either NF-kB or ERK/p38 MAPK down regulation thereby inhibiting B16F10 cell migration. Therefore, we proposed that CME-1 might be developed as a therapeutic potential candidate for the treatment of cancer metastasis.
Thanasekaran
T
Jayakumar
Chong-Chi
CC
Chiu
Shwu-Huey
SH
Wang
Duen-Suey
DS
Chou
School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Yung-Kai
YK
Huang
Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
Joen-Rong
JR
Sheu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D062610:Fungal Polysaccharides / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D025282:Mycelium / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D062610:Fungal Polysaccharides; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1