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).
Korotchkina
Lioubov G
LG
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA. Blagosklonny@oncotarget.com
Demidenko
Zoya N
ZN
Gudkov
Andrei V
AV
Blagosklonny
Mikhail V
MV
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