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Updated: Jul 11, 2025

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation
Shiina Suzuki1, Shun Saito1, Yuki Narushima1
1Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
Abstract:
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.
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