M.W. Roomi, N.W. Roomi, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, Oncology Division, 1260 Memorex Drive, Santa Clara, CA
Presented at:
48th Annual Meeting of the Society of Toxicology, Baltimore, Maryland, March 15-19, 2009
Published in:
The Toxicologists (suppl Toxicological Sciences) Abstract #1683, p 349, 2009.
Abstract
Introduction:
Chondrosarcoma, a malignant tumor of cartilaginous origin, primarily affects the cartilage cells of femur, arm, pelvis, knee and spine. The second most frequent primary malignant tumor of bone, it represents approximately 25% of primary osseous neoplasms. Incidence of tumors in children is low. Most tumors occur in patients older than 40 years. Cancer mortality usually results from tumor invasion of local tissues and metastases to vital organs. A novel nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has exhibited significant anticancer activity against a number of cancer cell lines, including inhibition of invasive parameters.
Objective:
We investigated the effect of NM on human chondrosarcoma cell line SW 1353 for viability, MMP expression, invasion, apoptosis and morphology.
Methods:
Human chondrosarcoma cell line SW1353 (ATCC) was grown in DEM media with 10% FBS and antibiotics and treated with NM at 0, 10, 50, 100, 500 and 1000 µg/ml in triplicate at each dose. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) 100 ng/ml for MMP-9 induction. Cell proliferation was assayed by MTT assay, MMPs by zymography, invasion through Matrigel, apoptosis using live green caspase detection kit, and morphology by H&E staining.
Results:
NM was not toxic to chondrosarcoma cell line at 100 µg/ml, but exhibited 10% and 40% toxicity at 500 and 1000 µg/ml. Zymography demonstrated two bands corresponding to MMP-2 and MM-9. PMA treatment enhanced MMP-9 secretion. NM inhibited the secretion of both MMP-2 and MMP-9 by 50% at 100 µg/ml and by 100% at 500 µg/ml. Invasion through Matrigel was inhibited by 40%, 50%, 70% and 100% at 50, 100, 500 and 1000 µg/ml respectively. NM induced slight apoptosis at 250 µg/ml, moderate at 500 µg/ml and significant at 1000 µg/ml. H&E showed slight changes at the highest concentration.
Conclusions:
NM significantly inhibited MMP secretion, invasion through Matrigel and apoptosis, important parameters for cancer prevention, suggesting NM has the potential for therapeutic use in treatment of chondrosarcoma.
Comment
Chondrosarcoma, a malignant tumor of cartilaginous origin, is the second most frequent primary malignant tumor of bone. Cancer mortality usually results from tumor invasion of local tissues and metastases to vital organs. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are associated with tumor invasion and metastasis. We investigated the effect of a nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract on human chondrosarcoma cell line SW 1353 for viability, MMP expression, invasion, apoptosis and morphology. Zymography demonstrated MMP-2 and MM-9 secretion with enhanced MMP-9 activity with PMA treatment. NM inhibited the secretion of both MMP-2 and MMP-9 by 50% at 100 µg/ml and by 100% at 500 µg/ml. Invasion through Matrigel was inhibited by 40%, 50%, 70% and 100% at 50, 100, 500 and 1000 µg/ml respectively. NM induced slight apoptosis at 250 µg/ml, moderate at 500 µg/ml and significant at 1000 µg/ml. These results are significant since they suggest that the nontoxic NM has potential for treatment of chondrosarcoma.
