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Titolo:
Coordinate involvement of cell cycle arrest and apoptosis strengthen the effect of FTY720
Autore:
Nagahara, Y; Matsuoka, Y; Saito, K; Ikekita, M; Higuchi, S; Shinomiya, T;
Indirizzi:
Natl Childrens Med Res Ctr, Div Res Promot, Setagaya Ku, Tokyo 1548509, Japan Natl Childrens Med Res Ctr Tokyo Japan 1548509 Ku, Tokyo 1548509, Japan Sci Univ Tokyo, Fac Sci & Technol, Dept Appl Biol Sci, Noda, Chiba 2788510, Japan Sci Univ Tokyo Noda Chiba Japan 2788510 l Sci, Noda, Chiba 2788510, Japan Showa Univ, Sch Pharmaceut Sci, Lab Biopharmaceut, Shinagawa Ku, Tokyo 1428555, Japan Showa Univ Tokyo Japan 1428555 aceut, Shinagawa Ku, Tokyo 1428555, Japan
Titolo Testata:
JAPANESE JOURNAL OF CANCER RESEARCH
fascicolo: 6, volume: 92, anno: 2001,
pagine: 680 - 687
SICI:
0910-5050(200106)92:6<680:CIOCCA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA STRAND BREAKS; RETINOBLASTOMA PROTEIN; DIFFERENTIAL REGULATION; KINASE-ACTIVITY; G(1) ARREST; PHOSPHORYLATION; INDUCTION; DEATH; ACTIVATION; INHIBITOR;
Keywords:
FTY720; cell cycle arrest; apoptosis; retinoblastoma protein; lymphoma cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Shinomiya, T Natl Childrens Med Res Ctr, Div Res Promot, Setagaya Ku, 3-35-31 Taishido,Tokyo 1548509, Japan Natl Childrens Med Res Ctr 3-35-31 Taishido Tokyo Japan 1548509
Citazione:
Y. Nagahara et al., "Coordinate involvement of cell cycle arrest and apoptosis strengthen the effect of FTY720", JPN J CANC, 92(6), 2001, pp. 680-687

Abstract

A novel reagent, FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrorhloride), has been shown to induce a significant decrease of lymphocytes and lymphoma cells and is expected to be a potent immunosuppressant and anti-tumor drug. The decrease in lymphocytes and lymphoma cells is mainly the result of FTY720-indured apoptosis, FTY720 directly affects mitochondria and induces cell death. Moreover, FTY720 activates protein phosphatase IPP) 2A and affects anti-apoptotic intracellular signal transduction proteins to attenuate the anti-apoptotic effect. III this study, we examined the relationship between FTY720-induced apoptosis and cell cycle regulation. FTY720 induced apoptosis significantly at the G0/G1 phase and caused G0/G1 cell cycle arrest of the human lymphoma cell lines HL-60RG and Jurkat, Simultaneously, retinoblastoma protein (pRB) was dephosphorylated, suggesting that dephosphorylation of pRB was related to FTY720-inductd G0/G1 cell cycle arrest. Because this dephosphorylation was completely blocked by a specific PP1/2A inhibitor, okadaic acid, it appears that FTY720-artivated PP2A is essential for FTY720-induccd cell cycle arrest. FTY720-induced apoptosis was inhibited by Bcl-2 overexpression in Jurkat cells, but this did not preventFTY720-induced cell cycle arrest, suggesting that the mechanism of FTY720-induced cell cycle arrest is independent of the mechanism of FTY720-inducedapoptosis, These two independent pathways strengthen the effect of FTY720.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 06:20:27