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Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.
Suzuki, Shiina; Saito, Shun; Narushima, Yuki; Kodani, Shunta; Kagaya, Noritaka; Suenaga, Hikaru; Shin-Ya, Kazuo; Arai, Midori A.
Affiliation
  • Suzuki S; Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
  • Saito S; Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
  • Narushima Y; Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
  • Kodani S; Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
  • Kagaya N; Technology Research Association for Next Generation Natural Products Chemistry, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Suenaga H; National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Shin-Ya K; National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Arai MA; Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan. midori_arai@bio.keio.ac.jp.
J Antibiot (Tokyo) ; 77(1): 30-38, 2024 01.
Article in En | MEDLINE | ID: mdl-37938761
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Calcineurin Limits: Humans Language: En Journal: J Antibiot (Tokyo) Year: 2024 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Calcineurin Limits: Humans Language: En Journal: J Antibiot (Tokyo) Year: 2024 Document type: Article Affiliation country: