2003 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	14370607
Research Institution	Meikai University
Principal Investigator	坂上宏明海大学, 歯学部, 教授 (50138484)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	(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。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Kawase M et al.: "Biological activity of persimmon (Diospyros Kaki) peel extracts."Phytotherapy Res. 17. 495-500 (2003)
[Publications] 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)
[Publications] 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)
[Publications] Watanabe K et al.: "Bufadienolide and Spirostanol glycosides from the Rhizomes of Helleborus orientalis."J.Nat.Prod.. 66. 236-241 (2003)
[Publications] Mimaki Y et al.: "Novel polygenated glycosides from the Rhizomes of Helleborus orientalis."Hel.Chim.Acta.. 86. 398-407 (2003)
[Publications] Fujisawa S et al.: "Interaction between 2-ethoxybenzoic acid (EBA) and eugenol, and its cytotoxicity."J Dental Res. 82. 43-47 (2003)
[Publications] Fujii H et al.: "Mitochondrial control of cell death induction by sodium 5,6-benzylidene-L-ascorbate."Anticancer Res. 23. 1353-1356 (2003)
[Publications] Hitosugi N et al.: "Comparative analysis of apoptosis-inducing activity of codeine and codeinone."Anesthesiology. 98. 643-650 (2003)
[Publications] 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)
[Publications] Osorio JN et al.: "Diospolysaponin A, a new polyoxygenated, spirostanol saponin from the tubers of Dioscorea Polygonoides."Heterocycles. 60. 1709-1715 (2003)
[Publications] Kuroda M et al.: "Bulbinelonesides A-E, phenylanthraquinone glycosides from the roots of Bulbinella floribunda."J Nat Product. 66. 894-897 (2003)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Kawase M et al.: "Structure-cytotoxic activity relationships of simple hydroxylated coumarins."Anticancer Res. 23. 3243-3246 (2003)
[Publications] Kawase M et al.: "Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity."In vivo. 17. 509-512 (2003)
[Publications] Fukai T et al.: "Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra."Fitoterapia. 74. 624-629 (2003)
[Publications] Fukai T et al.: "Anti-nephritis and radical scavenging activity of prenylfiavonoids."Fitoterapia. 74. 720-724 (2003)
[Publications] Tokunaga T et al.: "Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 3719-3726 (2003)
[Publications] Ori K et al.: "Lanosterol and tetralanosterol gycosides from the bulbs of Muscari Paradoxum."Phytochemistry. 64. 1351-1359 (2003)
[Publications] Morshed SRM et al.: "Effect of antitumor agents on cytotoxicity induction by sodium fluoride."Anticancer Res. 23. 4729-4736 (2003)
[Publications] Tokunaga T et al.: "Effect of endodontic agents on cytotoxicity induction by sodium fluoride."In vivo. 17. 582-592 (2003)
[Publications] 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)
[Publications] Wakabayashi H et al.: "Cytotoxic activity of tropolones against human oral tumor cell lines."Anticancer Res. 23. 4757-4764 (2003)
[Publications] Wakabayashi H et al.: "Cytotoxic activity of azulenes against human oral tumor cell lines."Anticancer Res. 23. 4747-4756 (2003)
[Publications] Nakamura C et al.: "Changes in intracellular concentrations of polyamines during apoptosis of HL-60 cells."Anticancer Res. 23. 4797-4804 (2003)
[Publications] Okayasu H et al.: "Comparison of cytotoxicity and radical scavenging activity between tea extracts and Chinese medicines."In vivo. 17. 577-582 (2003)
[Publications] Saito M et al.: "Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)."Anticancer Res. 23. 4693-4702 (2003)
[Publications] Kurihara T et al.: "Heterocyclic Chemistry. (Edited by D.C.Gautam)"RESA Publishers. 10 (2004)

2003 Fiscal Year Annual Research Report

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

Principal Investigator

坂上 宏 明海大学, 歯学部, 教授 (50138484)

Research Products

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

[Publications] 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)

[Publications] 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)

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

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

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

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

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

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

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

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

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

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

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

[Publications] 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)

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

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

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

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

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

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

坂上宏明海大学, 歯学部, 教授 (50138484)