0638 Induction of Apoptosis in Human Oral Tumor Cell Lines by Polyphenols
H. SAKAGAMI1, K. HASHIMOTO1, F. SUZUKI1, F. TAKAYAMA1, K. SATOH2, T. OGIWARA1, and S. FUJISAWA1, 1 Meikai University School of Dentistry, Saitama, Japan, 2 Showa University, Tokyo, Japan

Objective: Lignins are amorphous oxidized polymers of phenylpropenoids covalently bound to cellulose and hemicellulose in the cell walls, and have been reported to display antitumor, antiviral and antimicrobial activities. We investigated here the apoptosis-inducing activity of lignin against human oral tumor cell lines, in comparison with that of phenylpropenoid monomers, epigallocatechin gallate (EGCG) and gallic acid. Methods: Lignin was isolated by acid precipitation of NaOH extract of pine cone of Pinus parviflora Sieb. et Zucc. Human oral tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG), normal cells (human gingival fibroblast HGF), and mouse macrophage-like cells Raw 264.7 were cultured in DMEM + 10% FBS. The relative cell number was determined by MTT method, apoptosis induction by DNA fragmentation and caspase activation, nitric oxide (NO) production by Griess method, citrulline (CIT) production by amino acid analyzer, radical intensity by ESR spectroscopy. Results: Lignins showed very weak, but tumor-specific cytotoxic activity, and synergistically stimulated the apoptosis induction and radical generation by vitamin C or vitamin K3. EGCG and gallic acid showed higher apoptosis-inducing activity and radical intensity than lignin, but counteracted with those of vitamin C. Lignin stimulated the production of NO and CIT by Raw 264.7 cells to comparable level attained by LPS, whereas phenylpropenoid monomers, EGCG or gallic acid rather inhibited the LPS-stimulated NO production. Conclusion: These data suggest that lignin induces antitumor activity by its tumor-specific cytotoxic action and activation of cytocidal macrophages. Higher order structure of phenylpropenoid polymers complexed with carbohydrate moiety may be required for induction of such unique biological activity of lignin. Lignin and its related polyphenols may be applicable for the chemoprevention of oral cancer.

Seq #71 - Oral Tissues, Pharmacology
11:00 AM-12:15 PM, Thursday, 26 June 2003 Svenska Massan Exhibition Hall B

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