Current treatment of
osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other
cancers with
chemotherapy. Therefore, new, safe and effective treatment strategies are needed. We investigated the effect of a unique mixture of nutrients containing
lysine,
proline,
arginine,
ascorbic acid, and
epigallocatechin gallate (EGCG) on human
osteosarcoma cell lines U-2OS,
MNNG-HOS, and
Ewing's sarcoma SK-ES-1 by measuring: cell proliferation, expression of
matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. Cell proliferation was evaluated by MTT assay,
matrix metalloproteinases (
MMP) expression by
gelatinase zymography,
VEGF expression by ELISA, and invasion through
Matrigel. Cells were also treated with
phorbol 12-myristate 13-acetate (PMA) to study enhanced
MMP and
VEGF expression. The invasion of
osteosarcoma U-2OS and
MNNG-HOS cells through
Matrigel was significantly reduced in a dose-dependent fashion, with 100% inhibition of invasion of U-2OS cells at 100 microg/ml, and
MNNG cells at 50 microg/ml concentration of the synergistically acting nutrient mixture.
Ewing's sarcoma SK-ES-1 cells were not invasive. Nutrient synergy (NS) exhibited a dose response antiproliferative effect on
osteosarcoma U-2OS cells, reaching 67% at 1000 microg/ml of NS; no significant suppression of cell proliferation was seen with
MNNG or
Ewing's sarcoma cells. Zymography showed dose-dependent inhibition of
MMP secretion by all three cell lines in the presence of NS.
VEGF secretion by U-2OS cells was completely blocked at 500 microg/ml of NS. Our results suggest NS is an excellent candidate for
therapeutic use in the treatment of
osteosarcoma, by inhibiting
cancer cell invasion, and secretion of
MMPs and
VEGF, all critical parameters for
cancer control and prevention.