caa a22 4500 46325614X CHVBK 20180405153355.0 cr unu---uuuuu 170326e20070301xx s 000 0 eng 10.1007/s00277-006-0205-2 doi (NATIONALLICENCE)springer-10.1007/s00277-006-0205-2 Downregulation of cyclooxygenase-2 expression and activation of caspase-3 are involved in peroxisome proliferator-activated receptor-γ agonists induced apoptosis in human monocyte leukemia cells in vitro [Elektronische Daten] [Jia-Jun Liu, Pei-Qing Liu, Dong-Jun Lin, Ruo-Zhi Xiao, Min Huang, Xu-Dong Li, Yi He, Ren-Wei Huang] Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a transcription factor important in fat metabolism and PPAR-γ agonists were recently demonstrated to affect proliferation, differentiation, and apoptosis of different cell types. In the present study, two PPAR-γ agonists, 15-deoxy-delta (12,14)-prostaglandin J2 (15d-PGJ2) and a synthetic PPAR-γ agonist troglitazone (TGZ), were used to investigate activated PPAR-γ-induced apoptosis on human monocyte leukemia U937 and Mono Mac 6 cells in vitro. The results showed that both U937 and Mono Mac 6 cells demonstrated constitutive activation of COX-2 expression; treatment by 15d-PGJ2 and TGZ could induce apoptosis remarkably in human monocyte leukemia cells by disruption of mitochondrial membrane potential, activation of caspase-3, and causing cleavage of the caspase substrate poly (ADP-ribose) polymerase (PARP). Further studies revealed that treatment by both 15d-PGJ2 and TGZ remarkably downregulated COX-2 expression in these two kind of monocyte leukemia cells as measured by reverse transcriptase PCR (RT-PCR) and Western blot. Furthermore, the expression of Bcl-2 and Bcl-Xl and Mcl-1 was downregulated while Bax expression was upregulated concurrently after the cells were treated by these two agonists, and no variations were found in other Bcl-2 family members such as Bak, Bid, and Bad. Taken together, our results demonstrate for the first time that downregulation of cyclooxygenase-2 expression, disruption of mitochondrial membrane potential, activation of caspase-3, downregulation of Bcl-2, Bcl-Xl, and Mcl-1, and upregulation of Bax are involved in PPAR-γ agonists-induced apoptosis in these two human monocyte leukemia cells. Springer-Verlag, 2006 Peroxisome proliferator-activated receptor-γ (PPAR-γ) nationallicence Cyclooxygenase-2 (COX-2) nationallicence Bcl-2 nationallicence Human monocyte leukemia cell nationallicence Liu Jia-Jun Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut Liu Pei-Qing Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Zhongshan Road 2, 510080, Guangzhou, People's Republic of China aut Lin Dong-Jun Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut Xiao Ruo-Zhi Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut Huang Min Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Zhongshan Road 2, 510080, Guangzhou, People's Republic of China aut Li Xu-Dong Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut He Yi Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut Huang Ren-Wei Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut Annals of Hematology Springer-Verlag 86/3(2007-03-01), 173-183 0939-5555 86:3<173 2007 86 277 https://doi.org/10.1007/s00277-006-0205-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00277-006-0205-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Jia-Jun Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Liu Pei-Qing Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Zhongshan Road 2, 510080, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Lin Dong-Jun Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Xiao Ruo-Zhi Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Huang Min Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Zhongshan Road 2, 510080, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Li Xu-Dong Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- He Yi Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Huang Ren-Wei Department of Hematology and Oncology, Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 6000, 510630, Guangzhou, People's Republic of China aut NATIONALLICENCE 773 0- Annals of Hematology Springer-Verlag 86/3(2007-03-01), 173-183 0939-5555 86:3<173 2007 86 277 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer