2. Academic Validation
  3. Teleocidin B-4, a PKC Activator, Upregulates Hypoxia-Inducible Factor 1 (HIF-1) Activity by Promoting the Accumulation of HIF-1α Protein via the PKCα/mTORC Signaling Pathway

Teleocidin B-4, a PKC Activator, Upregulates Hypoxia-Inducible Factor 1 (HIF-1) Activity by Promoting the Accumulation of HIF-1α Protein via the PKCα/mTORC Signaling Pathway

  • J Nat Prod. 2024 Jun 28;87(6):1666-1671. doi: 10.1021/acs.jnatprod.4c00395.
Shogo Iseki 1,  Hiroaki Ikeda 1,  Sayaka Kobayashi 1,  Kazuhiro Irie 2,  Hiroshi Harada 3,  Hideaki Kakeya 1
Affiliations

Affiliations

  • 1 Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 2 Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
  • 3 Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
PMID: 38840407 DOI: 10.1021/acs.jnatprod.4c00395
Abstract

Hypoxia-inducible factor 1 (HIF-1) signaling is upregulated in an oxygen-dependent manner under hypoxic conditions. Activation of HIF-1 signaling increases the expression of HIF-1 target genes involved in cell survival, proliferation, and angiogenesis. Therefore, compounds that activate HIF-1 signaling have therapeutic potential in ischemic diseases. Screening for compounds that activate HIF-1 activity identified a microbial metabolite, teleocidin B-4, a PKC Activator. Other PKC activators, such as TPA and 10-Me-Aplog-1, also activated HIF-1 activity. PKC activators induced HIF-1α protein accumulation through PKCα/mTORC activation. These results suggest that PKC activators without tumor-promoting activity have potential as therapeutic agents via HIF-1 target gene activation.

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