Related Experiment Video

Updated: May 21, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Methylprednisolone induces apoptosis by interacting with the JAK/STAT pathway in HL-60 and K-562 leukemic cells

Burçin Tezcanli Kaymaz1, Nur Selvi, Güray Saydam

  • 1Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey. burcin.tezcanli@ege.edu.tr

Hematology (Amsterdam, Netherlands)
|June 6, 2012
PubMed
Abstract

Insights

High-dose methylprednisolone (MP) treatment significantly decreased STAT5A mRNA in leukemia cells. Protein level changes in STAT5A and STAT5B suggest complex JAK/STAT pathway involvement in MP-induced apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The JAK/STAT pathway is crucial in cellular processes, including immune response and cell proliferation.
  • Dysregulation of the JAK/STAT pathway is implicated in various hematological malignancies.
  • Methylprednisolone (MP) is a corticosteroid used in treating certain leukemias, but its precise molecular mechanisms are not fully elucidated.

Purpose of the Study:

  • To investigate the gene expression profiles of JAK/STAT pathway members STAT3, STAT5A, and STAT5B.
  • To analyze these profiles at both mRNA and protein levels in HL-60 and K-562 leukemia cells.
  • To understand their role in apoptosis induced by high-dose MP treatment.

Main Methods:

  • HL-60 and K-562 leukemia cell lines were treated with MP at their respective IC(50) values.
  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine mRNA expression levels of STAT3, STAT5A, and STAT5B.
  • Western blot analysis and Annexin V staining were employed to assess protein levels and apoptosis, respectively.

Main Results:

  • STAT5A mRNA expression significantly decreased at 48 hours post-MP treatment in both cell lines (P < 0.05).
  • Other STATs showed minor downregulation at the mRNA level.
  • While K-562 cells exhibited no significant protein expression changes, HL-60 cells showed STAT5A downregulation and STAT5B upregulation at 96 hours.

Conclusions:

  • JAK/STAT pathway components are likely involved in MP-induced apoptosis in HL-60 and K-562 leukemia cells.
  • Post-translational modifications may contribute to the observed protein expression changes, particularly in HL-60 cells.
  • The study highlights the complex role of STAT proteins in leukemia cell apoptosis following MP treatment.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.