Methylprednisolone induces apoptosis by interacting with the JAK/STAT pathway in HL-60 and K-562 leukemic cells
Makaleler > Tam Makale · 2012
Yazarlar: Burçin KAYMAZ, Nur SELVİ GÜNEL, Güray SAYDAM, Fahri ŞAHİN, Buket KOSOVA
Hematology, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2012, cilt 17, ss 93-99
DOI: 10.1179/102453312x13221316477859
Özet
OBJECTIVE: To determine the gene expression profiles of the JAK/STAT pathway members STAT3, STAT5A, STAT5B at both mRNA and protein levels in HL-60 and K-562 leukemia cells that were undergoing apoptosis following high-dose methylprednisolone (MP) treatment. METHODS: HL-60 cells were treated with 0.1 mM MP and K-562 cells were treated with 0.4 mM MP according to their IC(50) values. STAT3, STAT5A, and STAT5B mRNA relative expression levels were determined by qRT-PCR whereas the protein levels were detected via western-blot analysis and apoptosis was evaluated by Annexin V method. RESULTS: A significant decrease was seen in STAT5A mRNA relative expression level at 48 hours of MP treatment (P < 0.05) both in HL-60 and K-562 cells. Other STATs showed a lower downregulation in their relative expressions at 48 hours at mRNA level for both of the cell lines. STAT proteins showed no expression change in K-562 cells in time course experiments but while STAT5A expression was downregulated; STAT5B showed an increase at 96 hours in HL-60 cells. Apoptosis was triggered by high-dose MP treatment that was evaluated by fluorescent microscopy. CONCLUSION: The JAK/STAT pathway components may play an important role in the apoptosis mechanism of leukemic cells under MP treatment in HL-60 and K-562 cells. Other pathways may also be involved with a post-translational modification seen in the HL-60 cell line, with both upregulation and downregulation of protein expression levels of STAT5B and STAT5A, respectively.