Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients

Green tea polyphenols (TEA) are known to exhibit antioxidative activity as well as tumor-suppressing activity. In order to examine the tumor-suppressi ng activity of TEA against adult T-cell leukemia (ATL), me cultivated perip heral blood T lymphocytes of ATL patients (ATL PBLs), an HTLV-I-infected T- cell line (KODV) and healthy controls (normal PBLs) for 3 days in the prese nce of TEA and its main constituent, epigallocatechin-3-gallate (EGCg), to measure cell proliferation and apoptosis, and to quantitate mRNAs of HTLV-I pX and beta-actin genes of the cultured cells. Growth of ATL PBLs was sign ificantly inhibited by 9-27 mu g/ml of TEA and EGCg, in contrast to minimal growth inhibition of T cells of normal PBLs. Inhibition of KODV was interm ediate between ATL PBLs and normal PBLs. The ATL PBLs and KODV treated with 27 mu g/ml of either TEA or EGCg induced apoptotic DNA fragmentation, prod ucing terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end l abeling (TUNEL)-positive cells, while the normal PBLs treated with the same concentration of TEA or EGCg produced a negligibly small number of TUNEL-p ositive cells, in which apoptotic DNA fragmentation was not detectable, Exp ression of HTLV-I pX mRNA was suppressed more than 90% in ATL PBLs by treat ment with 3-27 mu g/ml of either TEA or EGCg, while expression of beta-acti n mRNA was much less suppressed by treatment with the same concentration of TEA or EGCg, These results indicate that TEA and EGCg inhibit growth of AT L PBLs, as well as HTLV-I-infected T-cells, by suppressing HTLV-I pX gene e xpression and inducing apoptotic cell death.