Epigallocatechin gallate protects U937 cells against nitric oxide-induced cell cycle arrest and apoptosis

Ingesting phenolic phytochemicals in many plant products may promote health , but the effects of phenolic phytochemicals at the cellular level have not been fully examined. Thus, it was determined if the tea phenolic phytochem ical, epigallocatechin gallate (EGCG), protects U937 human pro-monocytic ce lls against the nitrogen free radical, nitric oxide (. NO). Cells were incu bated for 4-6 h with 500 muM S-nitrosoglutathione (GSNO), which generates . NO, but this did not induce single-strand breaks in DNA. Nevertheless, 82 +/- 4% of GSNO-treated cells, compared to only 39 +/- 1% of untreated cells , were arrested in the G(1)-phase of the cell cycle. However, dosing the GS NO-treated cells with 9, 14, or 18 mug/ml of EGCG resulted in only 74 +/- 8 %, 66 +/- 1%, and 43 +/- 3% of the cells, respectively, in the G(1)-phase. Exposing cells to GSNO also resulted in the emergence of a sub-G(1) apoptot ic cell population numbering 14 +/- 3%, but only 5 +/- 2%, 5 +/- 1%, and 2 +/- 0% upon dosing of the GSNO-treated cells with 9, 14, and 18 mug/ml of E GCG, respectively. Furthermore, exposing cells to GSNO resulted in greater cell surface binding of annexin V-FITC, but binding was 41-89% lower in GSN O-treated cells dosed with EGCG. Collectively, these data suggest that . NO or downstream products induced cell cycle arrest and apoptosis that was no t due to single-strand breaks in DNA, and that EGCG scavenged cytotoxic . N O or downstream products, thus reducing the number of eel Is in a state of cell cycle arrest or apoptosis, J. Cell. Biochem, 81:647-658, 2001. (C) 200 1 Wiley-Liss, inc.