Effects of 15-deoxy-Delta12, 14 prostaglandin J2 and ciglitazone on human cancer cell cycle progression and death: the role of PPARgamma.
The role of PPARgamma in ciglitazone and 15-d PGJ(2)-induced apoptosis and cell cycle arrest of Jurkat (before and after PPARgamma gene silencing), U937 (express high levels of PPARgamma) and HeLa (that express very low levels of PPARgamma) cells was investigated. PPARgamma gene silencing, per se, induced a G2/M cell arrest, loss of membrane integrity and DNA fragmentation of Jurkat cells, indicating that PPARgamma is important for this cell survival and proliferation. Ciglitazone-induced apoptosis was abolished after knockdown of PPARgamma suggesting a PPARgamma-dependent pro-apoptotic effect. However, ciglitazone treatment was toxic for U937 and HeLa cells regardless of the presence of PPARgamma. This treatment did not change the cell cycle distribution corroborating with a PPARgamma-independent mechanism. On the other hand, 15-d PGJ(2) induced apoptosis of the three cancer cell lines regardless of the expression of PPARgamma. These results suggest that PPARgamma plays an important role for death of malignant T lymphocytes (Jurkat cells) and PPARgamma agonists exert their effects through PPARgamma-dependent and -independent mechanisms depending on the drug and the cell type.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Sao Paulo, Brazil.
Valéria
V
Ferreira-Silva
Alice Cristina
AC
Rodrigues
Thiago Dominguez Crespo
TD
Hirata
Sandro Massao
SM
Hirabara
Rui
R
Curi
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000502:physiology; D053938:DNA Fragmentation; D016195:G2 Phase / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D020298:U937 Cells
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D047495:PPAR gamma; D045162:Thiazolidinediones; D015230:Prostaglandin D2; C039671:ciglitazone