Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.
Shiina SuzukiShun SaitoYuki NarushimaShunta KodaniNoritaka KagayaHikaru SuenagaTeppei KawaharaMidori A AraiPublished in: The Journal of antibiotics (2023)
We screened a library of microbial extracts and compounds library using our constructed assay cells and found pulicatins F (1) and G (2), and cyclopiazonic acid (CPA) (3) as Notch activators. Pulicatin F (1) and (±)-pulicatin G were synthesized and their activities were evaluated. Notch activation of CPA (3) was investigated using Western blot and RT-PCR. CPA (3) increased protein level of HES1 and mRNA expression of HES1. Also, the expression of FMS-like tyrosine kinase 3 (FLT3), which was known to inhibit apoptosis, was also inhibited by CPA (3) addition. The Notch activation by CPA (3) and cytotoxicity against HL-60 were clearly canceled by addition of FK506, which is an inhibitor of calcineurin (CaN). In addition, it was revealed that CPA (3) induced apoptosis in HL-60 cells.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- tyrosine kinase
- cell cycle arrest
- oxidative stress
- signaling pathway
- cell proliferation
- epidermal growth factor receptor
- cell death
- acute myeloid leukemia
- south africa
- high throughput
- pi k akt
- mass spectrometry
- small molecule
- single cell
- inflammatory response
- nuclear factor
- high resolution