M.W. Roomi, N. Jariwalla, N.W. Roomi, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, Cancer Division, Santa Clara, CA 95050

Presented at: 
102nd Annual Meeting of the American Association for Cancer Research, Orlando, Florida, April 2-6, 2011.

Published in:
Proceedings of the 102nd Annual Meeting of the AACR, Vol 52, Abstract #1500, page 360

Abstract

Introduction: 
Fibrosarcoma, an aggressive and highly metastatic cancer of connective tissue, is generally associated with poor prognosis. Cancer mortality usually results from tumor invasion of local tissue and metastasis to vital organs. We investigated the effect of a specific nutrient mixture (PB) of quercetin, cruciferex, curcumin, green tea extract and resveratrol on human fibrosarcoma cell line HT-1080 for viability, MMP expression, invasion, apoptosis and morphology.

Material and Methods: 
Human fibrosarcoma cell line HT-1080 (ATCC) was cultured in DEM media, supplemented with 10% FBS and antibiotics in 24-well tissue plates. At near confluence, cells were treated with PB at 0, 10, 25, 50, 75 and 100 μg/mL, in triplicate at each dose. Cells were also treated with PMA (100 ng/mL) for MMP-9 induction. Cell proliferation was assayed by MTT assay, MMP by zymography, invasion through Matrigel, apoptosis using green caspase detection, and morphology by H&E staining.

Results: 
PB inhibited proliferation of human fibrosarcoma cells HT-1080 by 50% at 10 μg/mL, 60% at 25 μg/mL and 80% at 50-100 μg/mL, and inhibited the secretion of both MMP-2 and MMP-9 in a dose-dependent manner, with total inhibition at 50 μg/mL concentration. Invasion through Matrigel was inhibited 100% at 25 μg/mL PB. PB also induced apoptosis in a dose- dependent fashion. H&E staining showed slight morphological changes at higher concentrations.

Conclusion: 
These results suggest that PB is a potential therapeutic agent for fibrosarcoma, with potent anti-metastatic activity, because it inhibited fibrosarcoma cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and apoptosis, important parameters for cancer prevention.

Comment

Currently, there are no viable treatments for fibrosarcoma, an aggressive and highly metastatic cancer of connective tissue. The specific mixture (PB) of quercetin, cruciferex, curcumin, green tea extract and resveratrol had profound, significant anticancer effects on human fibrosarcoma cell line HT-1080 by inhibiting cell growth (by 80% at 50 μg/mL PB), MMP-2 and-9 secretion (with total inhibition at 50 μg/mL PB), and  invasion through Matrigel (100% block at 25 μg/mL PB). PB also induced fibrosarcoma cell apoptosis in a dose-dependent manner. These results suggest PB as a potential effective treatment for fibrosarcoma.