Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.
Mücahit VarlıSuresh R BhosleEunae KimYi Yangİsa TaşRui ZhouSultan PulatChathurika D B GamageSo-Yeon ParkHyung-Ho HaHangun KimPublished in: JACS Au (2024)
The anticancer therapeutic effects of usnic acid (UA), a lichen secondary metabolite, have been demonstrated in vitro and in vivo . However, the mechanism underlying the anticancer effect of UA remains to be clarified. In this study, the target protein of UA was identified using a UA-linker-Affi-Gel molecule, which showed that UA binds to the 14-3-3 protein. UA binds to 14-3-3, causing the degradation of proteasomal and autophagosomal proteins. The interaction of UA with 14-3-3 isoforms modulated cell invasion, cell cycle progression, aerobic glycolysis, mitochondrial biogenesis, and the Akt/mTOR, JNK, STAT3, NF-κB, and AP-1 signaling pathways in colorectal cancer. A peptide inhibitor of 14-3-3 blocked or regressed the activity of UA and inhibited its effects. The results suggest that UA binds to 14-3-3 isoforms and suppresses cancer progression by affecting 14-3-3 targets and phosphorylated proteins.
Keyphrases
- signaling pathway
- cell cycle
- cell proliferation
- papillary thyroid
- pi k akt
- oxidative stress
- squamous cell carcinoma
- epithelial mesenchymal transition
- induced apoptosis
- transcription factor
- squamous cell
- immune response
- amino acid
- protein protein
- high intensity
- inflammatory response
- endoplasmic reticulum stress
- childhood cancer