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Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A
Lioubov G Korotchkina1, Zoya N Demidenko, Andrei V Gudkov
1Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA. Blagosklonny@oncotarget.com
Abstract:
Cellular senescence is characterized by irreversible loss of proliferative potential and a large, flat cell morphology. Ectopic p21 and doxorubicin induced cellular senescence in HT1080 and WI-38-tert cell lines. In the same cell lines, the Mdm2 inhibitor nutlin-3a induced p53 but, unexpectedly, caused quiescence (reversible arrest) with a small cell morphology. We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy).
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