1994 Fiscal Year Annual Research Report

新規天然抗がん物質の探索

Research Project

Project/Area Number	06282105
Research Institution	The University of Tokyo
Principal Investigator	瀬戸治男東京大学, 分子細胞生物学研究所, 教授 (10013335)
Co-Investigator(Kenkyū-buntansha)	長田裕之理化学研究所, 抗生物質部, 主任研究員 (80160836) 小林昭雄岡山大学, 農学部, 教授 (30115844) 永井和夫東京工業大学, 生命理工学部, 教授 (00011974) 池上晋広島大学, 生物生産学部, 教授 (80011980) 岩崎成夫東京大学, 分子細胞生物学研究所, 教授 (00013326)
Keywords	抗癌物質 / cororubicin / menoxymycin / ustiloxin / jaspisin / isojaspisin / nostodione A / enamidonin
Research Abstract	本年度の各班員の成果は以下個別に列挙するとおりである。 1.P388白血病細胞に対して有効な抗癌物質として、放線菌の培養液からcororubicinおよびmenoxymycinを単離し、その生物活性についての検討を行った。 2.微小管の機能を阻害する環状ペプチドであるustiloxin類について、抗癌剤開発を目指したそれらの化学変換と生産菌の培養による生産法の検討をおこなった。 3.海綿から細胞融合を選択的に阻害するjaspisinならびにisojaspisinを単離した。今後、腫瘍細胞が分泌する細胞外マトリックス分解性メタロプロテアーゼに対する作用を詳しく解析する計画である。 4.リンパ球の活性化を誘導する物質を探索した結果、紅花花弁の熱抽出物に幼若化促進活性を認めた。本物質はB細胞の幼若化を選択的に誘導し、またIgM抗体の産生も促進した。活性成分は分子量100kD以上の多糖類である。 5.ウニ胚を用いた精密in vivoアッセイにより、陸生ラン藻から活性物質としてnostodione Aを得た。本化合物は特異なα-ジケトン構造を有する新規化合物である。 6.上皮増殖因子の新規阻害剤としてenamidoninを放線菌培養液から単離し、その化学構造を決定した。本化合物はマウスの正常表皮細胞Ba1b/MK細胞に対してEGF依存的な[3H]チミジンの取り込みを10μg/mlで50%阻害し、温度感受性腫瘍ウイルスでトランスフォームしたsrcts-NRK細胞の腫瘍形態を10〜31μg/mlで正常形態に復帰させる活性を示した。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] K.Ishigami: "Cororubicin,a new anthracycline antibiotic generating active oxygen in tumor cell." J.Antibiot.47. 1219-1225 (1994)
[Publications] Y.Koiso: "Ustiloxins,antimitotic cyclic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens." J.Antibiot.47. 801-809 (1994)
[Publications] M.Kamishohara: "Antitumor activity of SPMV III,a derivative of the nucleoside antibiotic spicamycin,against human tumor xenografts." J.Antibiot.47. 1305-1311 (1994)
[Publications] Y.Hayakawa: "Menoxymycins A nd B,new antitumor antibiotics generating active oxygen in tumor cells." J.Antibiot.47. 1344-1347 (1994)
[Publications] S.Ikegami: "Selective inhibition of exoplasmic membtane fusion in Echinoderm gametes with jaspisin,a novel antihatching substance." J.Biol.Chem.269. 23262-23267 (1994)
[Publications] S.Ohta: "Isojaspisin:a novel styryl sulfate from a marine sponge,Jaspissp.,that inhibits hatching of sea urchin embryos." Tetrahedron Lett.35. 4579-4580 (1994)
[Publications] T.Kataoka: "Acidification is essential for maintaining the structure and function of lytic qranules of CTL.Effect of concanamycin A," J.Immunol.154. 3938-3947 (1994)
[Publications] M.Ubukata: "Absolute configuration of reveromycin A,an inhibitor of the signal transduction of epidermal growth factor." J.Chem.Soc.Chem.Commun.1994. 1877-1878 (1994)
[Publications] A.Kobayashi: "Nostodione A,a novel mitotic spindle poison from a blue-green alga Nostoc Commune." Z.Naturforsch.49c. 464-470 (1994)
[Publications] Y.Ohshima: "A ;monogaractosyl diacylglycerol from a cultured marine dinoflagellate Scrippsiella trochoidea." J.Nat.Pord.57. 534-536 (1994)
[Publications] K.Matsunaga: "Cylindrene,a novel sesquiterpenoid from Imperata cylindrica with inhibitory activity on contractions of vascular smooth muscle." J.Nat.Pord.57. 1183-1184 (1994)
[Publications] S.Koshino: "A new cyclic lipopeptide antibiotic,enamidonin." J.Antibiot.48. 207-209 (1995)
[Publications] Y.Li: "Ustiloxins,new antitumor cyclic peptides:Interaction with porcine brain tubulin." Biochem.Pharmacol.48(in press). (1995)
[Publications] T.Kataoka: "Prodigiosin 25-C uncouples vacuolar type H^+-ATPase,inhibits vacuolar acidification and affect glycoprotein processing." FEBS lett.(in press). (1995)
[Publications] A.Kobayashi: "Antifungal compounds induced in the dual culture with phytolaccaamericana callus and Botrysis fabae." Z.Naturforsch.50c(in press). (1995)
[Publications] H.Sahara: "In vivo antitumor effect of lyso-sulfono-quinovosyl-diacylglyceride,derived from sea urchin intestine." Cancer Reseach. (submitted). (1995)

1994 Fiscal Year Annual Research Report

新規天然抗がん物質の探索

Principal Investigator

瀬戸 治男 東京大学, 分子細胞生物学研究所, 教授 (10013335)

Research Products

[Publications] K.Ishigami: "Cororubicin,a new anthracycline antibiotic generating active oxygen in tumor cell." J.Antibiot.47. 1219-1225 (1994)

[Publications] Y.Koiso: "Ustiloxins,antimitotic cyclic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens." J.Antibiot.47. 801-809 (1994)

[Publications] M.Kamishohara: "Antitumor activity of SPMV III,a derivative of the nucleoside antibiotic spicamycin,against human tumor xenografts." J.Antibiot.47. 1305-1311 (1994)

[Publications] Y.Hayakawa: "Menoxymycins A nd B,new antitumor antibiotics generating active oxygen in tumor cells." J.Antibiot.47. 1344-1347 (1994)

[Publications] S.Ikegami: "Selective inhibition of exoplasmic membtane fusion in Echinoderm gametes with jaspisin,a novel antihatching substance." J.Biol.Chem.269. 23262-23267 (1994)

[Publications] S.Ohta: "Isojaspisin:a novel styryl sulfate from a marine sponge,Jaspissp.,that inhibits hatching of sea urchin embryos." Tetrahedron Lett.35. 4579-4580 (1994)

[Publications] T.Kataoka: "Acidification is essential for maintaining the structure and function of lytic qranules of CTL.Effect of concanamycin A," J.Immunol.154. 3938-3947 (1994)

[Publications] M.Ubukata: "Absolute configuration of reveromycin A,an inhibitor of the signal transduction of epidermal growth factor." J.Chem.Soc.Chem.Commun.1994. 1877-1878 (1994)

[Publications] A.Kobayashi: "Nostodione A,a novel mitotic spindle poison from a blue-green alga Nostoc Commune." Z.Naturforsch.49c. 464-470 (1994)

[Publications] Y.Ohshima: "A ;monogaractosyl diacylglycerol from a cultured marine dinoflagellate Scrippsiella trochoidea." J.Nat.Pord.57. 534-536 (1994)

[Publications] K.Matsunaga: "Cylindrene,a novel sesquiterpenoid from Imperata cylindrica with inhibitory activity on contractions of vascular smooth muscle." J.Nat.Pord.57. 1183-1184 (1994)

[Publications] S.Koshino: "A new cyclic lipopeptide antibiotic,enamidonin." J.Antibiot.48. 207-209 (1995)

[Publications] Y.Li: "Ustiloxins,new antitumor cyclic peptides:Interaction with porcine brain tubulin." Biochem.Pharmacol.48(in press). (1995)

[Publications] T.Kataoka: "Prodigiosin 25-C uncouples vacuolar type H^+-ATPase,inhibits vacuolar acidification and affect glycoprotein processing." FEBS lett.(in press). (1995)

[Publications] A.Kobayashi: "Antifungal compounds induced in the dual culture with phytolaccaamericana callus and Botrysis fabae." Z.Naturforsch.50c(in press). (1995)

[Publications] H.Sahara: "In vivo antitumor effect of lyso-sulfono-quinovosyl-diacylglyceride,derived from sea urchin intestine." Cancer Reseach. (submitted). (1995)

瀬戸治男東京大学, 分子細胞生物学研究所, 教授 (10013335)