Cytotoxic activity of low molecular weight polyphenols against human oral tumor cell lines

A total of 150 chemically-defined natural and synthetic polyphenols (flavon oids, dibenzoylmethanes, dihydrostilbenes, dihydrophenanthrenes and 3-pheny lchromen-4-ones), with molecular weights ranging from 224 to 824, were inve stigated for cytotoxic activity against normal, tumor and human immunodefic iency virus (HIV)-infected cells. They showed higher cytotoxic activity aga inst human oral squamous cell carcinoma HSC-2 and salivary gland tumor HSG cell lines than against normal human gingival fibroblasts HGF. Many of the active compounds had a hydrophilic group (hydroxyl group) in the vicinity o f a hydrophobic group (prenyl, phenyl, methylcyclohexene or methylbenzene m oiety), similar to isoprenoid-substituted flavones. Substitution of hydroph obic group (prenyl or geranyl group) did not significantly change the cytot oxic activity of flavanones, isoflavans, chalcones or 5-hydroxy-3-phenoxych romen-4-ones. However, the prenylation(s) of art isoflavone and a 2-arylben zofuran significantly enhanced the cytotoxic activity. Agarose gel electrop horesis showed that active components induced internuleosomal DNA fragmenta tion in human promyelocytic leukemic HL-60 cells, but not in HSC-2 cells. M ost of the polyphenols failed to reduce the cytophathic effect of HIV infec tion in MT-4 cells.