Prevention of phosphatidylinositol 3'-kinase-Akt survival signaling pathway during topotecan-induced apoptosis.
作者： Ayako Nakashio , Susumu Rokudai , Naoya Fujita , Takashi Tsuruo , Saori Sato
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摘要: The serine/threonine kinase Akt (also known as protein B) is a downstream effector of phosphatidylinositol-3'-kinase [PI(3)K] that recognized the major mediator survival signals protect cells from undergoing apoptosis. In course examining target molecules topoisomerase I inhibitor topotecan, we found topotecan treatment promoted dephosphorylation led to inactivation in human lung cancer A549 cells. Transfection constitutively active akt cDNA into resulted reduction cytotoxic effect indicating inhibition pathway played an important role exhibition topotecan-mediated effects. Further analysis revealed suppressed upstream kinases Akt, 3-phosphoinositide-dependent 1, and PI(3)K. Overall, results demonstrate exhibited its effects by down-regulating PI(3)K-Akt signaling addition inhibiting I.
aacrjournals.org参考文章(39)
Scott H. Kaufmann, Phyllis A. Svingen, Steven D. Gore, Deborah K. Armstrong, Yung-Chi Cheng, Eric K. Rowinsky, Altered formation of topotecan-stabilized topoisomerase I-DNA adducts in human leukemia cells Blood. ,vol. 89, pp. 2098- 2104 ,(1997) , 10.1182/BLOOD.V89.6.2098
Pommier Y, Dubrez L, Genne P, Solary E, Goldwasser F, The role of cell cycle regulation and apoptosis triggering in determining the sensitivity of leukemic cells to topoisomerase I and II inhibitors. Leukemia. ,vol. 9, pp. 1013- 1024 ,(1995)
Alex Toker, Lewis C. Cantley, Signalling through the lipid products of phosphoinositide-3-OH kinase Nature. ,vol. 387, pp. 673- 676 ,(1997) , 10.1038/42648
Tetsuo Mashima, Zhihong Chen, Takashi Tsuruo, Mikihiko Naito, Activation of Actin-cleavable Interleukin 1β-converting Enzyme (ICE) Family Protease CPP-32 during Chemotherapeutic Agent-induced Apoptosis in Ovarian Carcinoma Cells Cancer Research. ,vol. 56, pp. 5224- 5229 ,(1996)
Shelly Wuerzberger, David A. Boothman, George Wilding, Paul Hutson, Dawn R. Church, Benjamin Frydman, Sarah M. Planchon, Donald T. Witiak, β-Lapachone-mediated Apoptosis in Human Promyelocytic Leukemia (HL-60) and Human Prostate Cancer Cells: A p53-independent Response Cancer Research. ,vol. 55, pp. 3706- 3711 ,(1995)
Dario R Alessi, Philip Cohen, Mechanism of activation and function of protein kinase B. Current Opinion in Genetics & Development. ,vol. 8, pp. 55- 62 ,(1998) , 10.1016/S0959-437X(98)80062-2
I. Plo, A. Bettaïeb, B. Payrastre, V. Mansat-De Mas, C. Bordier, A. Rousse, A. Kowalski-Chauvel, G. Laurent, D. Lautier, The phosphoinositide 3-kinase/Akt pathway is activated by daunorubicin in human acute myeloid leukemia cell lines. FEBS Letters. ,vol. 452, pp. 150- 154 ,(1999) , 10.1016/S0014-5793(99)00631-6
John F. R. Kerr, Clay M. Winterford, Brian V. Harmon, Apoptosis. Its significance in cancer and cancer Therapy Cancer. ,vol. 73, pp. 2013- 2026 ,(1994) , 10.1002/1097-0142(19940415)73:8<2013::AID-CNCR2820730802>3.0.CO;2-J
Bart Vanhaesebroeck, Sally J. Leevers, George Panayotou, Michael D. Waterfield, Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends in Biochemical Sciences. ,vol. 22, pp. 267- 272 ,(1997) , 10.1016/S0968-0004(97)01061-X
FRANK TRAGANOS, KAREN SEITER, ERIC FELDMAN, H. DOROTA HALICKA, ZBIGNIEW DARZYNKIEWICZ, Induction of apoptosis by camptothecin and topotecan. Annals of the New York Academy of Sciences. ,vol. 803, pp. 101- 110 ,(1996) , 10.1111/J.1749-6632.1996.TB26380.X