Inhibition of cell invasion and MMP production by a nutrient mixture in malignant liposarcoma cell line SW-872.
Liposarcoma, a malignancy of fat cells, is the most common soft tissue sarcoma. Though rare, poorly differentiated liposarcomas commonly metastasize to lungs and liver, leading to poor prognosis. Prevention of Extracellular matrix (ECM) degradation by inhibition of matrix metalloproteinases (MMPs) activity has been shown to be a promising therapeutic approach to inhibition of cancer progression. A nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has shown significant anticancer activity against a number of cancer cell lines. We investigated the effect of NM on liposarcoma cell line SW-872 proliferation (MTT assay), MMP secretion (gelatinase zymography), invasion through Matrigel, and apoptosis and morphology (live green caspase kit and H&E). Liposarcoma cell growth was inhibited by 36 and 61% at 500 and 1,000 microg/ml NM. Zymography demonstrated both MMP-2 and MMP-9 secretion, with PMA-enhanced MMP-9 activity. NM inhibited both MMPs with virtual total inhibition at 500 microg/ml NM. Invasion through Matrigel was inhibited at 100, 500, and 1,000 microg/ml by 44, 75, and 100%, respectively. Dose-dependent apoptosis of liposarcoma cells was evident with NM challenge, with virtually all cells exposed to 1,000 microg/ml NM in late apoptosis. H&E staining did not demonstrate any changes in morphology at lower concentrations. However, some apoptotic changes were evident at higher concentrations. In conclusion, NM significantly inhibited liposarcoma cell growth, MMP activity, and invasion and induced apoptosis in vitro-important parameters for cancer development, suggesting NM as a potential treatment strategy for liposarcoma.
Roomi
M W
MW
Cancer Division, Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
Ivanov
V
V
Kalinovsky
T
T
Niedzwiecki
Aleksandra
A
Rath
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology*; D028241:Camellia sinensis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004338:Drug Combinations; D018093:Gelatinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008080:Liposarcoma / Q000201:enzymology*; D008239:Lysine / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology
D000970:Antineoplastic Agents; D004338:Drug Combinations; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D018093:Gelatinases; D008239:Lysine; D001205:Ascorbic Acid