Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A.
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).
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA. Blagosklonny@oncotarget.com
Lioubov G
LG
Korotchkina
Zoya N
ZN
Demidenko
Andrei V
AV
Gudkov
Mikhail V
MV
Blagosklonny
D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D003114:Colony-Forming Units Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004358:Drug Therapy / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D015151:Immunoblotting; D010879:Piperazines / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001616:beta-Galactosidase
D050759:Cyclin-Dependent Kinase Inhibitor p21; D007093:Imidazoles; D010879:Piperazines; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3; D004317:Doxorubicin; D051736:Proto-Oncogene Proteins c-mdm2; D001616:beta-Galactosidase