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Effects of Natural Chemoprevention in Human Colon Ca Cells

Comparison of effects of natural chemopreventive agents on NF-kappaB activity in HT-29 human colon carcinoma cell line

Woo-Sik Jeong, In-Wha Kim, Rong Hu, Tony A.-N. Kong.

Rutgers University, School of Pharmacy, Piscataway, NJ.

Epidemiological studies have shown that certain components of fruits, vegetables, grains, and nuts may prevent or reduce the risk of some chronic diseases such as cancer.

For the last several decades numerous chemopreventive and/or chemotherapeutic compounds have been identified from natural products including foods and plants source. Of the naturally occurring chemopreventive compounds, isothiocyanates in cruciferous vegetables, polyphenols in green tea and red wine, and curcuminoids in turmeric have gained much attention.

The chemopreventive mechanisms of these compounds are, however, not fully understood. The transcription factor nuclear factor kappa B (NF-ęB) has been known to be a critical regulator of inflammation and apoptosis, and to play an important role in cancer development.

In the present study, the effects of several naturally occurring chemopreventive compounds on the transcription activation of NF-kappaB and the cell viability in a human colon cancer cell line (HT-29 cell) were evaluated. HT-29 cells were stably transfected with NF-kappaB-luciferase construct and stable clones were selected.

The cells were treated with various concentrations (up to 100 micro M) of natural chemopreventive agents for an hour before challenged with lipopolysaccharde (LPS). Luciferase activities were measured after 6 hours of incubation.

The chemopreventive agents used include isothiocyanates (sulforaphane, phenethyl- and allyl-isothiocyanates), polyphenolic compounds (epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, resveratrol, procyanidin B1 and B2), and curcumin. Of these compounds tested, phenethyl isothiocyanate and sulforaphane showed the most potent inhibitions against LPS-induced NF-kappaB luciferase activity in HT-29 cells while polyphenols exhibited little effects or slight activations on the activity at the given concentrations.

Isothiocyanates, curcumin, and EGCG also inhibited LPS-induced IBalpha phosphorylation. Phenethyl isothiocyanate (PEITC), sulforaphane and curcumin were the most potent inhibitors in the cell viability of HT-29 NF-kappaB transfectants.

These results suggest that natural chemopreventive agents may have different functions on NF-kappaB activity in the colon and/or colon cancer.

Future studies on the biological consequences by these natural agents are needed to elucidate the chemopreventive mechanisms involved.

AACR Abstract Number: R4930 2003


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