2003 年度実績報告書

歯科領域におけるポリフェノールの臨床的意義と応用に関する研究

研究課題

研究課題/領域番号	14370607
研究機関	明海大学
研究代表者	坂上宏明海大学, 歯学部, 教授 (50138484)
研究分担者	吉田隆志岡山大学, 薬学部, 教授 (20025696) 藤沢盛一郎明海大学, 歯学部, 教授 (40014162) 草間薫明海大学, 歯学部, 教授 (20130479) 河瀬雅美城西大学, 薬学部, 講師 (20112641) 三巻祥浩東京薬科大学, 薬学部, 助教授 (90229790)
キーワード	ポリフェノール / リグニン / 口腔癌 / アポトーシス / マクロファージ / NO / アスパラギン合成酵素 / 薬剤耐性
研究概要	(1)腫瘍選択性を示す物質を探索するために、多種のサンプルのヒト口腔癌細胞(口腔扁平上皮癌HSC-2、HSC-3、唾液腺腫瘍HSG)、ヒト前骨髄性白血病細胞(HL-60)や、ヒト正常細胞(歯肉細胞、歯根膜細胞、歯髄細胞)に対する細胞傷害活性を、MTT法を用いて検討した。アセロラのヘキサン抽出物のシリカゲルカラムクロマトグラフィー溶出分画が、腫瘍選択性と、MDR遺伝子を導入したL5178細胞におけるMDR活性を克服した。26種類のα、β-不飽和ケトン類の腫瘍選択性は一般的に低かった。8種類のヒドロキシケトン類の中で、deferiproneは特に、腫瘍選択性とアポトーシス(DNAの断片化、カスパーゼ3,8,9の活性化、アポトーシス抵抗性タンパク質Bcl-2の細胞内濃度の低下、ミトコンドリアの膜電位変化)誘導能に優れていた。この活性は鉄イオンにより減弱した。23種類のβ-ジケトン類は、中間の腫瘍選択性を示した。約100種のサポニンの腫瘍選択性は低かった。腫瘍選択性とアポトーシス誘導活性は必ずしも一致しなかった。半経験的分子軌道解析により、フラボノイドとスチルベンの腫瘍選択性は、log Pが3-4付近で最大になり、水和の安定性が0に近づくほど増大した。 (2)27種類のアズレン類、27種類のトロポロン類の中で、1,3-ジフルオロ体、2,4-ジブロム-7-メトキシ体は、LPSにより活性化したマウスマクロファージ様細胞Raw264.7によるNO産生を強く抑制した。その原因は、iNOS mRNAの発現および細胞内iNOSタンパク質の量の減少と、NOラジカルの消去であった。リグニンは、LPS同様マクロファージを活性化し、iNOS及びアスパラギン合成酵素(AS)の発現を促進した。ASの発現は、グルコース量に依存して変動した。現在、ASの発現の生理的意義を探るために、現在RNAi法を用いてAS遺伝子のノックダウンを検討中である。

研究成果
(30件)

すべてその他

すべて文献書誌 (30件)

[文献書誌] Kawase M et al.: "Biological activity of persimmon (Diospyros Kaki) peel extracts."Phytotherapy Res. 17. 495-500 (2003)
[文献書誌] Ori K et al.: "Norlanostane and lanostane glycosides from the bulbs of Chinodoxa luciliae and their cytotoxic activity."Chem Pharm Bull. 51. 92-95 (2003)
[文献書誌] Motohashi N et al.: "Cytotoxic and multidrug resistance reversal activity of a vegetable, 'Anastasia red', a series of sweet pepper"Phytotherapy Res. 17. 348-352 (2003)
[文献書誌] Watanabe K et al.: "Bufadienolide and Spirostanol glycosides from the Rhizomes of Helleborus orientalis."J.Nat.Prod.. 66. 236-241 (2003)
[文献書誌] Mimaki Y et al.: "Novel polygenated glycosides from the Rhizomes of Helleborus orientalis."Hel.Chim.Acta.. 86. 398-407 (2003)
[文献書誌] Fujisawa S et al.: "Interaction between 2-ethoxybenzoic acid (EBA) and eugenol, and its cytotoxicity."J Dental Res. 82. 43-47 (2003)
[文献書誌] Fujii H et al.: "Mitochondrial control of cell death induction by sodium 5,6-benzylidene-L-ascorbate."Anticancer Res. 23. 1353-1356 (2003)
[文献書誌] Hitosugi N et al.: "Comparative analysis of apoptosis-inducing activity of codeine and codeinone."Anesthesiology. 98. 643-650 (2003)
[文献書誌] Ogiwara T et al.: "Inhibition of NO production by activated macrophages by phenolcarboxylic acid monomers and polymers with radical scavenging activity."Anticancer Res. 23. 1317-1324 (2003)
[文献書誌] Osorio JN et al.: "Diospolysaponin A, a new polyoxygenated, spirostanol saponin from the tubers of Dioscorea Polygonoides."Heterocycles. 60. 1709-1715 (2003)
[文献書誌] Kuroda M et al.: "Bulbinelonesides A-E, phenylanthraquinone glycosides from the roots of Bulbinella floribunda."J Nat Product. 66. 894-897 (2003)
[文献書誌] Ishihara M, Sakagami H: "Application of semiempirical method to estimate the cytotoxic activity of gallic acid and its related compounds."Anticancer Res. 23. 2549-2552 (2003)
[文献書誌] Hitosugi N et al.: "Analysis of apoptosis signaling pathway in human cancer cell lines by codeinone, a synthetic derivative of codeine."Anticancer Res. 23. 2569-2576 (2003)
[文献書誌] Hatsukari I et al.: "Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines."Anticancer Res. 23. 2413-2418 (2003)
[文献書誌] Wakabayashi H et al.: "Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by Barbados cherry, a fruit of Malpighia emarginata DC."Anticancer Res. 23. 3237-3242 (2003)
[文献書誌] Kawase M et al.: "Structure-cytotoxic activity relationships of simple hydroxylated coumarins."Anticancer Res. 23. 3243-3246 (2003)
[文献書誌] Kawase M et al.: "Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity."In vivo. 17. 509-512 (2003)
[文献書誌] Fukai T et al.: "Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra."Fitoterapia. 74. 624-629 (2003)
[文献書誌] Fukai T et al.: "Anti-nephritis and radical scavenging activity of prenylfiavonoids."Fitoterapia. 74. 720-724 (2003)
[文献書誌] Tokunaga T et al.: "Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 3719-3726 (2003)
[文献書誌] Ori K et al.: "Lanosterol and tetralanosterol gycosides from the bulbs of Muscari Paradoxum."Phytochemistry. 64. 1351-1359 (2003)
[文献書誌] Morshed SRM et al.: "Effect of antitumor agents on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 4729-4736 (2003)
[文献書誌] Tokunaga T et al.: "Effect of endodontic agents on cytotoxicity induction by sodium fluoride."In vivo. 17. 582-592 (2003)
[文献書誌] 横須賀章人ら: "タシロイモ科植物Tacca chantrieriの化学成分と細胞毒性活性"薬学雑誌. 123 suppl.3. 54-57 (2003)
[文献書誌] Wakabayashi H et al.: "Cytotoxic activity of tropolones against human oral tumor cell lines."Anticancer Res. 23. 4757-4764 (2003)
[文献書誌] Wakabayashi H et al.: "Cytotoxic activity of azulenes against human oral tumor cell lines."Anticancer Res. 23. 4747-4756 (2003)
[文献書誌] Nakamura C et al.: "Changes in intracellular concentrations of polyamines during apoptosis of HL-60 cells."Anticancer Res. 23. 4797-4804 (2003)
[文献書誌] Okayasu H et al.: "Comparison of cytotoxicity and radical scavenging activity between tea extracts and Chinese medicines."In vivo. 17. 577-582 (2003)
[文献書誌] Saito M et al.: "Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)."Anticancer Res. 23. 4693-4702 (2003)
[文献書誌] Kurihara T et al.: "Heterocyclic Chemistry. (Edited by D.C.Gautam)"RESA Publishers. 10 (2004)

2003 年度 実績報告書

歯科領域におけるポリフェノールの臨床的意義と応用に関する研究

研究代表者

坂上 宏 明海大学, 歯学部, 教授 (50138484)

研究成果

[文献書誌] Kawase M et al.: "Biological activity of persimmon (Diospyros Kaki) peel extracts."Phytotherapy Res. 17. 495-500 (2003)

[文献書誌] Ori K et al.: "Norlanostane and lanostane glycosides from the bulbs of Chinodoxa luciliae and their cytotoxic activity."Chem Pharm Bull. 51. 92-95 (2003)

[文献書誌] Motohashi N et al.: "Cytotoxic and multidrug resistance reversal activity of a vegetable, 'Anastasia red', a series of sweet pepper"Phytotherapy Res. 17. 348-352 (2003)

[文献書誌] Watanabe K et al.: "Bufadienolide and Spirostanol glycosides from the Rhizomes of Helleborus orientalis."J.Nat.Prod.. 66. 236-241 (2003)

[文献書誌] Mimaki Y et al.: "Novel polygenated glycosides from the Rhizomes of Helleborus orientalis."Hel.Chim.Acta.. 86. 398-407 (2003)

[文献書誌] Fujisawa S et al.: "Interaction between 2-ethoxybenzoic acid (EBA) and eugenol, and its cytotoxicity."J Dental Res. 82. 43-47 (2003)

[文献書誌] Fujii H et al.: "Mitochondrial control of cell death induction by sodium 5,6-benzylidene-L-ascorbate."Anticancer Res. 23. 1353-1356 (2003)

[文献書誌] Hitosugi N et al.: "Comparative analysis of apoptosis-inducing activity of codeine and codeinone."Anesthesiology. 98. 643-650 (2003)

[文献書誌] Ogiwara T et al.: "Inhibition of NO production by activated macrophages by phenolcarboxylic acid monomers and polymers with radical scavenging activity."Anticancer Res. 23. 1317-1324 (2003)

[文献書誌] Osorio JN et al.: "Diospolysaponin A, a new polyoxygenated, spirostanol saponin from the tubers of Dioscorea Polygonoides."Heterocycles. 60. 1709-1715 (2003)

[文献書誌] Kuroda M et al.: "Bulbinelonesides A-E, phenylanthraquinone glycosides from the roots of Bulbinella floribunda."J Nat Product. 66. 894-897 (2003)

[文献書誌] Ishihara M, Sakagami H: "Application of semiempirical method to estimate the cytotoxic activity of gallic acid and its related compounds."Anticancer Res. 23. 2549-2552 (2003)

[文献書誌] Hitosugi N et al.: "Analysis of apoptosis signaling pathway in human cancer cell lines by codeinone, a synthetic derivative of codeine."Anticancer Res. 23. 2569-2576 (2003)

[文献書誌] Hatsukari I et al.: "Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines."Anticancer Res. 23. 2413-2418 (2003)

[文献書誌] Wakabayashi H et al.: "Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by Barbados cherry, a fruit of Malpighia emarginata DC."Anticancer Res. 23. 3237-3242 (2003)

[文献書誌] Kawase M et al.: "Structure-cytotoxic activity relationships of simple hydroxylated coumarins."Anticancer Res. 23. 3243-3246 (2003)

[文献書誌] Kawase M et al.: "Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity."In vivo. 17. 509-512 (2003)

[文献書誌] Fukai T et al.: "Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra."Fitoterapia. 74. 624-629 (2003)

[文献書誌] Fukai T et al.: "Anti-nephritis and radical scavenging activity of prenylfiavonoids."Fitoterapia. 74. 720-724 (2003)

[文献書誌] Tokunaga T et al.: "Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 3719-3726 (2003)

[文献書誌] Ori K et al.: "Lanosterol and tetralanosterol gycosides from the bulbs of Muscari Paradoxum."Phytochemistry. 64. 1351-1359 (2003)

[文献書誌] Morshed SRM et al.: "Effect of antitumor agents on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 4729-4736 (2003)

[文献書誌] Tokunaga T et al.: "Effect of endodontic agents on cytotoxicity induction by sodium fluoride."In vivo. 17. 582-592 (2003)

[文献書誌] 横須賀章人ら: "タシロイモ科植物Tacca chantrieriの化学成分と細胞毒性活性"薬学雑誌. 123 suppl.3. 54-57 (2003)

[文献書誌] Wakabayashi H et al.: "Cytotoxic activity of tropolones against human oral tumor cell lines."Anticancer Res. 23. 4757-4764 (2003)

[文献書誌] Wakabayashi H et al.: "Cytotoxic activity of azulenes against human oral tumor cell lines."Anticancer Res. 23. 4747-4756 (2003)

[文献書誌] Nakamura C et al.: "Changes in intracellular concentrations of polyamines during apoptosis of HL-60 cells."Anticancer Res. 23. 4797-4804 (2003)

[文献書誌] Okayasu H et al.: "Comparison of cytotoxicity and radical scavenging activity between tea extracts and Chinese medicines."In vivo. 17. 577-582 (2003)

[文献書誌] Saito M et al.: "Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)."Anticancer Res. 23. 4693-4702 (2003)

[文献書誌] Kurihara T et al.: "Heterocyclic Chemistry. (Edited by D.C.Gautam)"RESA Publishers. 10 (2004)

2003 年度実績報告書

坂上宏明海大学, 歯学部, 教授 (50138484)