Vitamin E TPGS 1000 Induces Apoptosis in the K562 Cell Line: Implications for Chronic Myeloid Leukemia.
Jazmin Calvo-AlvarezMarlene Jimenez-Del-RioCarlos Velez-PardoPublished in: Oxidative medicine and cellular longevity (2021)
Chronic myeloid leukemia (CML) is a hematologic malignancy derived from the myeloid lineage molecularly characterized by t(9;22)(q34;q11) resulting in BCR-ABL1 gene fusion, which is known as Philadelphia (Ph) chromosome. Although tyrosine kinase inhibitors (TKIs) have restored and maintained the quality of life of patients with CML, an important minority of patients become resistant to first-and-second-generation TKIs and require an alternative treatment. The K562 cell (Ph+, p53-/-) line was treated with Vit E TPGS 1000 (20-80 μM) only or with other products of interest (e.g., antioxidant N-acetylcysteine (NAC), specific JNK and caspase-3 inhibitor SP600125, and NSCSI, respectively) for 24 h at 37°C. Cells were analyzed by fluorescence microscopy (FM), flow cytometry (FC), and Western blotting (WB) techniques. We show that TPGS induces apoptosis in K562 cells through H2O2 signaling mechanism comprising the activation of a minimal molecular cascade: the kinase JNK>the transcription factor c-JUN>the activation of BCL-only BH3 proapoptotic protein PUMA>loss of mitochondrial membrane potential (ΔΨ m)>activation of caspase-3>chromatin condensation>fragmentation of DNA. Additionally, TPGS oxidizes the stress sensor protein DJ-1-Cys106-SH into DJ-1-Cys106-SO3 and arrested the cell cycle in the S phase. Remarkably, NAC, SP600125, and NSCSI blocked TPGS-induced OS and apoptosis in K562. Since TPGS is safe in mice and humans, it is especially promising for preclinical and clinical CML leukemia research. Our findings support the view that oxidation therapy offers an important opportunity to eliminate CML.
Keyphrases
- chronic myeloid leukemia
- induced apoptosis
- oxidative stress
- transcription factor
- endoplasmic reticulum stress
- cell cycle arrest
- cell death
- cell cycle
- signaling pathway
- single molecule
- diabetic rats
- flow cytometry
- end stage renal disease
- cell therapy
- dna damage
- chronic kidney disease
- single cell
- cell proliferation
- bone marrow
- newly diagnosed
- pi k akt
- genome wide
- prognostic factors
- acute myeloid leukemia
- copy number
- dna binding
- ejection fraction
- genome wide identification
- type diabetes
- acute lymphoblastic leukemia
- hydrogen peroxide
- high resolution
- circulating tumor
- risk assessment
- peritoneal dialysis
- optical coherence tomography
- dendritic cells
- metabolic syndrome
- south africa
- mesenchymal stem cells
- high glucose
- binding protein
- climate change
- adipose tissue
- skeletal muscle
- cell free
- high throughput
- insulin resistance