Cytotoxic activity of low molecular weight polyphenols against human oral tumor cell lines.
A total of 150 chemically-defined natural and synthetic polyphenols (flavonoids, dibenzoylmethanes, dihydrostilbenes, dihydrophenanthrenes and 3-phenylchromen-4-ones), with molecular weights ranging from 224 to 824, were investigated for cytotoxic activity against normal, tumor and human immunodeficiency virus (HIV)-infected cells. They showed higher cytotoxic activity against 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 of a hydrophobic group (prenyl, phenyl, methylcyclohexene or methylbenzene moiety), similar to isoprenoid-substituted flavones. Substitution of hydrophobic group (prenyl or geranyl group) did not significantly change the cytotoxic activity of flavanones, isoflavans, chalcones or 5-hydroxy-3-phenoxychromen-4-ones. However, the prenylation(s) of an isoflavone and a 2-arylbenzofuran significantly enhanced the cytotoxic activity. Agarose gel electrophoresis showed that active components induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 cells. Most of the polyphenols failed to reduce the cytophathic effect of HIV infection in MT-4 cells.
Fukai
T
T
Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan. fukai@phar.toho-u.ac.jp
Sakagami
H
H
Toguchi
M
M
Takayama
F
F
Iwakura
I
I
Atsumi
T
T
Ueha
T
T
Nakashima
H
H
Nomura
T
T
D019380:Anti-HIV Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005419:Flavonoids; D006801:Humans; D008970:Molecular Weight; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D059808:Polyphenols