M.W. Room, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Medical Oncology 2007, 24: 394-401

Abstract:
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 µg/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 µg/ml NM. Invasion through Matrigel was inhibited at 100, 500, and 1,000 µg/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 µg/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.

Key Words:
Liposarcoma, MMPs, Matrigel invasion, Nutrients, Green tea extract, Ascorbic acid, Lysine