Comparative effects of naturally-occuring chemopreventive compounds on metastasis-related events in HT-1080 cells

Proc Amer Assoc Cancer Res, Volume 46, 2005 2463 Metastasis, the spreading of a tumor to vital organs, is one of the main causes of mortality in cancer patients. The process of metastasis involves an intricate interplay between altered cell adhesion, survival, proteolysis, migration and lymph/angiogenesis. In recent years, naturally occurring agents, e.g,, epigallocatechin gallate (EGCG), curcumin, resveratrol and others, have shown promise for the prevention of several types of cancer. Most of the studies have been done on the effect of these compounds on tumorigenesis, without significant emphasis on their effect on metastasis. The aim of the present study was to evaluate certain chemopreventive compounds for their potential to interfere with metastasis-related events, and to understand the molecular mechanism underlying their antimetastatic effect. In this study five compounds, namely EGCG, curcumin, resveratrol, phenyl isothiocyanate (PITC), and diallyl trisulfide (DTS) were examined, for their effect on cell adhesion, motility, invasion, and secretion of MMP-9 in HT-1080 cells. Serum-starved cells were treated with chemopreventive agents for 24 hr and invasion, adhesion, motility, and MMP-9 secretion were measured by matri-gel invasion, binding to collagen membrane, wound healing assay, and Western blot analysis, respectively. All the compounds exhibited a significant dose-dependent inhibitory effect on invasion, motility, and MMP-9 secretion and a dose-dependent stimulatory effect on cell adhesion. The order of inhibition by these compounds at 100 μM concentration was as follows: Invasion: EGCG > curcumin > DTS > resveratrol > PITC; cell motility: resveratrol > PITC > EGCG > DTS > curcumin; MMP-9 secretion: resveratrol > EGCG > curcumin > PITC > DTS. At a concentration of 20 μM, PITC, EGCG, DTS, and resveratrol stimulated cell adhesion by 135, 61, 32, and 10% respectively. Curcumin at this concentration showed no effect on cell adhesion. The data from these studies clearly demonstrate that these chemopreventive compounds have the potential to prevent tumor metastasis. Work is in progress to understand the mechanisms underlying the action of these compounds.