The mechanism of suppression of NF-κB activity and survivin expression by sodium arsenite in ATL cells

• Project/Area Number: 19790239
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kagoshima University
• Principal Investigator: CHE Xiao-fang Kagoshima University, 大学院・医歯学総合研究科, 助教 (10437973)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: ATL / survivin / NF-κB / sodium arsenite / XIAP / dimer

Research Abstract

成人T細胞白血病(ATL)は抗癌剤治療抵抗性が高いため、予後は極めて不良である。我々は、アポトーシスを抑制する因子であるsurvivinがATL、特に急性型ATLに高発現することとヒ素はATL細胞のsurvivin発現レベルを低下させることを見出した。Survivinの発現は、ATL細胞の抗癌剤耐性の一つの要因と考えられ、ATL治療の標的分子として注目されている。今回の研究で、ヒ素がIκB-αの分解を抑制することによって、NF-κBの核への移行を阻害し、NF-κBを介するsurvivinの転写を抑制し、ATL細胞のアポトーシスを誘導したことは明らかにした。また、SurvivinがXIAPと結合する部位(15-38aa)を標的としたオリゴペプチドはATL細胞株S1TとMT2の細胞増殖を抑制し、アポトーシスを誘導することを見出した。このペプチドによるATL細胞のアポトーシス誘導のメカニズムを解明すれば、ATLの新しい治療法の開発に貢献できると考えている。

Research Products

• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives (2008)
  • Author(s): Che X-F, Akiyama S, Tomoda A
  • Journal Title: Oncol Rep 19 Pages: 1253-1258
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase inhibits the expression of proapoptic protein BNIP3 (2008)
  • Author(s): Ikeda R, Che X-F(他14名4番目)
  • Journal Title: Biochem Biophys Res Commun. 370 Pages: 220-224
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one (2008)
  • Author(s): Shirato K, Che X-F(他6人6番目)
  • Journal Title: Biol Pharm Bull 31 Pages: 62-67
  • NAID: 110006569975
  • Peer Reviewed
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in KM12C cells. (2008)
  • Author(s): Zhao H-Y, Che X-F(他13名8番目)
  • Journal Title: Cancer Lett. 270 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Hyperosmotic Stress Up-regulates the Expression of Major Vault Protein in SW620 Human Colon Cancer Cells (2008)
  • Author(s): Ikeda R, Che X-F(他17名10番目)
  • Journal Title: Exp. Cell Res. 314 Pages: 3017-3026
  • Peer Reviewed
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU. (2008)
  • Author(s): Zhao H-Y, Che X-F(他13名8番目)
  • Journal Title: Cancer Res. 68 Pages: 7035-7041
  • Peer Reviewed
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU (2008)
  • Author(s): Hong-Ye Zhao
  • Journal Title: Cancer Res 68 Pages: 7035-7041
  • Peer Reviewed
• [Journal Article] Hyperosmotic Stress Up-regulates the Expression of Major Vault Protein in SW620 Human Colon Cancer Cells (2008)
  • Author(s): Ryuji Ikeda
  • Journal Title: Exp Cell Res 314 Pages: 3017-3026
  • Peer Reviewed
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in KM12C cells (2008)
  • Author(s): Hong-Ye Zhao
  • Journal Title: Cancer Lett 270 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives (2008)
  • Author(s): Xiao-Fang Che
  • Journal Title: Oncol Rep 19 Pages: 1253-1258
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase inhibits the expression of proapoptic protein BNIP3 (2008)
  • Author(s): Ryuji Ikeda
  • Journal Title: Biochem Biophys Res Commun 370 Pages: 220-224
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one (2008)
  • Author(s): Ken Shirato
  • Journal Title: Biol Pharm Bull 31 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Apoptosis induction preceded by mitochondrial depolarization in multiple myeloma cell line U266 by 2-aminophenoxazine-3-one. (2008)
  • Author(s): Shirato K
  • Journal Title: Biol Pharm Bull. 31(1) Pages: 62-67
  • Peer Reviewed
• [Journal Article] Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells (2007)
  • Author(s): Tachiwada T, Che X-F(他11人3番目)
  • Journal Title: Oncol Rep 18 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Copper-Transporting P-Type ATPase, ATP7A, Confers Multidrug Resistance and Its Expression Is Related to Resistance to SN-38 in Clinical Colon Cancer. (2007)
  • Author(s): Owatari S, Che X-F(他13人中6番目)
  • Journal Title: Cancer Res. 67 Pages: 4860-4868
  • Peer Reviewed
• [Journal Article] Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells. (2007)
  • Author(s): Tachiwada T
  • Journal Title: Oncol Rep. 18 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer. (2007)
  • Author(s): Owatari S
  • Journal Title: Cancer Res 67 Pages: 4860-4868
  • Peer Reviewed
• [Journal Article] Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives
  • Author(s): Che X-F
  • Journal Title: Oncol Rep. (In press)
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3.
  • Author(s): Ikeda R
  • Journal Title: Biochem Biophys Res Commun. (In press)
  • Peer Reviewed
• [Presentation] survivinペプチド(89-104アミノ酸)によるATL細胞のアポトーシス誘導 (2008)
  • Author(s): 車暁芳
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 低酸素によるヒト線維芽細胞でのPGISの高発現 (2008)
  • Author(s): 王嘉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] チミジンホスホリラーゼ発現腫瘍細胞におけるNF-κBを介したIL-8の発現亢進機講 (2008)
  • Author(s): 田畑祥
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] ヒト大腸癌における5-FUによる血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 趙紅業
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] survivinペプチド(89-104アミノ酸)によるATL細胞のアポトーシス誘導 (2008)
  • Author(s): 車暁芳
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 低酸素によるヒト線維芽細胞でのPGISの高発現 (2008)
  • Author(s): 王嘉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] チミジンボスホリラーゼ発現腫瘍細胞におけるNF-κBを介したIL-8の発現亢進機講 (2008)
  • Author(s): 田畑祥
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] Thymidine phosphorylase suppresses the expression of proapoptic protein BNIP3 (2007)
  • Author(s): Ryuji Ikeda
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] The effect of hypoxia on gene expression in human fibroblast WI-38 cells (2007)
  • Author(s): Xiao-Fang Che
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Increased expression of PGIS in two human fibroblast cell lines under hypoxic condition (2007)
  • Author(s): Jia Wang
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Induction of angiogenesis inhibitor thrombospondin-1 by 5-FU in human colon cancer cells (2007)
  • Author(s): Hong-Ye Zhao
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Molecular basis for the induction of interleukin-8 by thmidine phosphorylase (2007)
  • Author(s): Sho Tabata
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] The effect of hypoxia on gene expression in human fibroblast WI-38 cells (2007)
  • Author(s): Xiao-fang Che
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Increased expression of PGIS in two human fibroblast cell lines under hypoxic condition. (2007)
  • Author(s): Jia Wang
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Thymidine Phosphorylase Suppresses the Expression of Proapoptotic Protein BNIP3 (2007)
  • Author(s): Ryuji Ikeda
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Induction of angiogenesis inhibitor thrombospondin-1 by 5-FU in human colon cells (2007)
  • Author(s): Hong-ye Zhao
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Molecular basis for the induction of interleukin-8 by thymidine phosphorylase (2007)
  • Author(s): Sho Tabata
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03