2002 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 / 口腔癌 / アポトーシス / マクロファージ / アスパラギン / NO / 薬剤耐性 / 薬物代謝酵素
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、唾液腺腫瘍細胞HSG)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法を用いて比検討した。その結果、3,5-dibenzoyl-1,4-dihydropyridines, trifluoromethyl ketones(TF1,TF2,TF3)、アセロラ(投稿中)、もぐさの抽出液(シリカゲルカラム-ODSカラムによる部分精製標品)、サポニン、テルペン類、キウイ抽出液、ヒマラヤの薬草、ビワ葉成分、コデイノンが腫瘍選択的な細胞傷害活性を示した。また、3,5-dibenzoyl-1,4-dihydropyridinesやアセロラ抽出物(投稿中)は、対照で用いたベラパミル以上の薬剤耐性MDR克服活性を示した。 2)TF1-3、もぐさ成分、コデイノン、ヒマラヤの薬草などは、癌細胞にアポトーシス(ヌクレオソーム単位のDNAの断片化、カスパーゼの活性化、シトクロムCの放出)を誘導した。 3)ポリフェノールのうち、松かさ由来リグニンは、リポ多糖(LPS)と同様に、マウスマクロファージを活性化して、NO、シトルリン、そして新たに我々が見いだしたアスパラギン(ASN)の産生を促進した。これらの物質によるASNの産生促進は、一部ASN合成酵素の発現の促進であることが判明した。結合部位の同定を行なう予定である。これに対して、タンニンはフラボノイド類は、LPSのマクロファージ活性化のNO産生を抑制した。その原因は、NOの合成酵素の細胞内含量の若干の低下と、NO消去活性(ESRを用いて測定)であった。 4)ポリフェノールの肝細胞癌HepG2と口腔癌細胞(HSC-2)に対する感受性の比較を行なったところ、前者の方がより抵抗性を示した。ラット肝臓初代培養細胞や、CYP遺伝子を導入したHepG2細胞を用いて、ポリフェノールによるCYPの誘導を検討する予定である。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Kawase M et al.: "3,5-dibenzoyl-1,4-dihvdropyridines : Synthesis and MDR reversal in tumor cells"Bioorg Med Chem. 10. 1051-1055 (2002)
[Publications] Watanabe K et al.: "Cycloartane glycosides from the Rhizomes of Cimjicifuga racemosa and their cytotoxic activities"Chem Pharm Bull. 50. 121-125 (2002)
[Publications] Taniguchi S et al.: "Production of bioactive triterpenes by Eriobotyra Japonica calli"Phytochemistry. 59. 315-323 (2002)
[Publications] Yokosuka A et al.: "New diarylheptanoids and diaryheptanoid glucosides from Rhizomes of Tacca chantrieri and their cytotoxic activity"J Nat Prod. 65. 283-289 (2002)
[Publications] Tashiro M et al.: "Effects of prenylflavones from Sophora species on growth and activation of mouse macrophage-like cell lines"Anticancer Res. 22. 53-58 (2002)
[Publications] Hitosugi N et al.: "Induction of cell death by pro-oxidant action of Moxa smoke"Anticancer Res. 22. 159-164 (2002)
[Publications] Suzuki F et al.: "Stimulation of arginine consumption and asparagine production in LPS-activated macrophages"Anticancer Res. 22. 203-210 (2002)
[Publications] Miyamoto M et al.: "Tumor-specificity and radical scavenging activity of poly-herbal formula"Anticancer Res. 22. 1217-1224 (2002)
[Publications] Kawase M et al.: "Biological activity of persimmon (Diospyros Kaki) peel extracts"Phytotherapy Res. (印刷中). (2002)
[Publications] Fujisawa S et al.: "Antioxidant and prooxidant action of eugenol-related compounds and their cytotoxicity"Toxicology. 177. 39-54 (2002)
[Publications] Kuroda M et al.: "Lucilianosides A and B, two novel tetranor-lanostane hexaglycosides from the bulbs of Chionodoxa luciliae"Tetrahedrone. 58. 6735-6740 (2002)
[Publications] Motohashi N et al.: "Cancer prevention and therapy with Kiwifruit in Chinese folklore medicine : a study of kiwifruit extracts"J EthonoPharmacol. 81. 357-364 (2002)
[Publications] Tashiro M et al.: "Effects of isoflavones from Sophora species on growth and activation of mouse macrophage-like cell line"Anticancer Res. 22. 2185-2192 (2002)
[Publications] Suzuki F et al.: "Effect of lignins and their precursors on nitric oxide, citrulline and asparagines production by mouse macrophage-like cells Raw 264.7"Anticancer Res. 22. 2719-2724 (2002)
[Publications] Miyamoto M et al.: "Effect of poly-herbal formula on NO production by LPS-stimulated mouse macrophage-like cells"Anticancer Research. 22. 3293-3302 (2002)
[Publications] Mimaki Y et al.: "Spirostanol pentaglycosides fron the underground parts of Polianthes tuberosa"J Nat Prod. 65. 1424-1428 (2002)
[Publications] Mimaki Y et al.: "Steroidal glycosides from the leaves of Cestrum nocturnum"J Nat Prod. 65. 1863-1868 (2002)
[Publications] 吉田隆志: "ビワ葉の抗腫瘍性成分"バイオインダストリー. 20. 27-33 (2003)

2002 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.: "3,5-dibenzoyl-1,4-dihvdropyridines : Synthesis and MDR reversal in tumor cells"Bioorg Med Chem. 10. 1051-1055 (2002)

[Publications] Watanabe K et al.: "Cycloartane glycosides from the Rhizomes of Cimjicifuga racemosa and their cytotoxic activities"Chem Pharm Bull. 50. 121-125 (2002)

[Publications] Taniguchi S et al.: "Production of bioactive triterpenes by Eriobotyra Japonica calli"Phytochemistry. 59. 315-323 (2002)

[Publications] Yokosuka A et al.: "New diarylheptanoids and diaryheptanoid glucosides from Rhizomes of Tacca chantrieri and their cytotoxic activity"J Nat Prod. 65. 283-289 (2002)

[Publications] Tashiro M et al.: "Effects of prenylflavones from Sophora species on growth and activation of mouse macrophage-like cell lines"Anticancer Res. 22. 53-58 (2002)

[Publications] Hitosugi N et al.: "Induction of cell death by pro-oxidant action of Moxa smoke"Anticancer Res. 22. 159-164 (2002)

[Publications] Suzuki F et al.: "Stimulation of arginine consumption and asparagine production in LPS-activated macrophages"Anticancer Res. 22. 203-210 (2002)

[Publications] Miyamoto M et al.: "Tumor-specificity and radical scavenging activity of poly-herbal formula"Anticancer Res. 22. 1217-1224 (2002)

[Publications] Kawase M et al.: "Biological activity of persimmon (Diospyros Kaki) peel extracts"Phytotherapy Res. (印刷中). (2002)

[Publications] Fujisawa S et al.: "Antioxidant and prooxidant action of eugenol-related compounds and their cytotoxicity"Toxicology. 177. 39-54 (2002)

[Publications] Kuroda M et al.: "Lucilianosides A and B, two novel tetranor-lanostane hexaglycosides from the bulbs of Chionodoxa luciliae"Tetrahedrone. 58. 6735-6740 (2002)

[Publications] Motohashi N et al.: "Cancer prevention and therapy with Kiwifruit in Chinese folklore medicine : a study of kiwifruit extracts"J EthonoPharmacol. 81. 357-364 (2002)

[Publications] Tashiro M et al.: "Effects of isoflavones from Sophora species on growth and activation of mouse macrophage-like cell line"Anticancer Res. 22. 2185-2192 (2002)

[Publications] Suzuki F et al.: "Effect of lignins and their precursors on nitric oxide, citrulline and asparagines production by mouse macrophage-like cells Raw 264.7"Anticancer Res. 22. 2719-2724 (2002)

[Publications] Miyamoto M et al.: "Effect of poly-herbal formula on NO production by LPS-stimulated mouse macrophage-like cells"Anticancer Research. 22. 3293-3302 (2002)

[Publications] Mimaki Y et al.: "Spirostanol pentaglycosides fron the underground parts of Polianthes tuberosa"J Nat Prod. 65. 1424-1428 (2002)

[Publications] Mimaki Y et al.: "Steroidal glycosides from the leaves of Cestrum nocturnum"J Nat Prod. 65. 1863-1868 (2002)

[Publications] 吉田隆志: "ビワ葉の抗腫瘍性成分"バイオインダストリー. 20. 27-33 (2003)

坂上宏明海大学, 歯学部, 教授 (50138484)