Mechanism of G1-like arrest by low concentrations of paclitaxel: next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis.

作者: Z N Demidenko , S Kalurupalle , C Hanko , C-u Lim , E Broude

DOI: 10.1038/ONC.2008.82

关键词: ImmunologyCell cycleGrowth factor receptorMicrotubuleCell fate determinationInterphaseCarcinogenesisCell biologyMitosisApoptosisBiology

摘要: Paclitaxel (PTX) and other microtubule inhibitors cause mitotic arrest. However, low concentrations of PTX (low PTX) paradoxically G1 arrest (without arrest). Here, we demonstrated that unexpectedly, did not in the first cell cycle prevent cells from passing through S phase entering mitosis. Mitosis was prolonged but still divided, producing either two or three (tripolar mitosis), thus explaining a sub peak caused by PTX. Importantly, were viable non-apoptotic. Some fused back then progressed to mitosis, frequently again before becoming arrested next cell-cycle interphase. Thus, postmitotic second even third cycles. By increasing concentration PTX, tripolar mitosis transformed slippage, eliminating peak. Time-lapse microscopy revealed ensured p53-dependent We conclude directly affects only duration determines fate, including G1-like

参考文章(33)
Batia Stark, Marta Jeison, Rima Gobuzov, Hagit Krug, Leticia Glaser-Gabay, Drorit Luria, Ronit El-Hasid, Miriam Ben Harush, Gali Avrahami, Salvador Fisher, Jerry Stein, Rina Zaizov, Isaac Yaniv, Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploid line: detection by fluorescence in situ hybridization. Cancer Genetics and Cytogenetics. ,vol. 128, pp. 108- 113 ,(2001) , 10.1016/S0165-4608(01)00411-3
David M. Prescott, Cellular Sites of RNA Synthesis Progress in Nucleic Acid Research and Molecular Biology. ,vol. 3, pp. 33- 57 ,(1964) , 10.1016/S0079-6603(08)60738-2
Jacques Pris, Danielle Clement, Pierre Colombies, Allégria Kessous, Near Haploid Cell Line in Lymphoid Blast Crisis of Ph1-positive Chronic Myeloid Leukemia Cancer Research. ,vol. 40, pp. 1354- 1359 ,(1980)
Wendell K, Jordan Ma, Wilson L, Copp H, Gardiner S, Derry Wb, Mitotic Block Induced in HeLa Cells by Low Concentrations of Paclitaxel (Taxol) Results in Abnormal Mitotic Exit and Apoptotic Cell Death Cancer Research. ,vol. 56, pp. 816- 825 ,(1996)
Shireen Hussain Khan, Geoffrey M Wahl, None, p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest Cancer Research. ,vol. 58, pp. 396- 401 ,(1998)
Mikhail V. Blagosklonny, Zbigniew Darzynkiewicz, H. Dorota Halicka, Piotr Pozarowski, Zoya N. Demidenko, James J. Barry, Kalpana R. Kamath, Robert A. Herrmann, Paclitaxel induces primary and postmitotic G1 arrest in human arterial smooth muscle cells. Cell Cycle. ,vol. 3, pp. 1050- 1056 ,(2004) , 10.4161/CC.3.8.986
Susan Band Horwitz, Mechanism of action of taxol Trends in Pharmacological Sciences. ,vol. 13, pp. 134- 136 ,(1992) , 10.1016/0165-6147(92)90048-B
Yumi Uetake, Greenfield Sluder, Cell-Cycle Progression without an Intact Microtubule Cytoskeleton Current Biology. ,vol. 17, pp. 2081- 2086 ,(2007) , 10.1016/J.CUB.2007.10.065
Mary Ann Jordan, Leslie Wilson, Microtubules as a target for anticancer drugs. Nature Reviews Cancer. ,vol. 4, pp. 253- 265 ,(2004) , 10.1038/NRC1317