| Co-Investigator(Kenkyū-buntansha) |
KUSAMA Kaoru Meikai University, School of Dentistry, Professor, 歯学部, 教授 (20130479)
FUJISAWA Sei-ichtro Meikai University, School of Dentistry, Professor, 歯学部, 教授 (40014162)
YOSHIDA Takashi Okayama University, School of Parmaceutical Sci, Prof, 薬学部, 教授 (20025696)
MIMAKI Yoshihiro Tokyo Univ. of Pharmacy and Life Science, Associate Prof., 薬学部, 助教授 (90229790)
KAWASE Masami Josai Univ., Sch. of Pharm. Sci., Assistant Professor, 薬学部, 講師 (20112641)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
A total of 374 compounds including plant polyphenols (such tannins, flavonoids and coumarins), terpenes, antitumor antibiotics and other organic compounds were investigated for their tumor-specific cytotoxicity. Tumor-specific index (TS value) was determined by the ratio of the 50% cytotoxic concentration (CC_<50>) of each compound against human oral normal cells (gingival fibroblast, pulp cells, periodontal ligament fibroblast) to that against human cancer cell lines (oral squamous cell carcinoma, salivary gland carcinoma, promyelocytic leukemic cells), after correction of the number of the normal and cancer cells. Flavones, flavonols (3-hydroxyflavones), isoprenoid-substituted flavonoids, benzophenones, xanthones, anthraquinones, phenylbutanone glucoside, stilbene glucoside, isoflavones, isoflavanones, stilbenes (TS=0.3-31.7), coumarin derivatives (TS=1.0->11.0), procyanidines and flavonoids (TS=1.0->7.4), hydrolysable tannins (TS=1.0-8.2), triterpene aglycones and glycosides (TS=0.65->2.8), cycloartane glycosides and chromones (TS=0.7-1.4), furostaol glycosides (TS=0.4->17.0), □,□-unsaturated ketones (TS=0.6-1.9), hydroxyketones (TS=1.0->17.6),□ -diketones (TS=0.3-6.3), styrylchromones (TS=1.4-27.3), dihydroisoxazole and isoxazole derivatives (TS=0.9-1.6) showed the intermediate range of tumor-specificity. On the other hand, doxorubicin (TS=255.0) and nocobactin NA-a, -b (TS=80.0, 43.9) showed significantly higher tumor-specificity. This cannot be simply explained by the difference of the expression of mdr 1 mRNA. There was no apparent relationship between the tumor-specificity and apoptosis-inducing activity. It is important to evaluate the tumor-specificity before the elucidation of the mechanism of apoptosis induction.
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