Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3.
Phytother Res
; 36(9): 3540-3554, 2022 Sep.
Article
de En
| MEDLINE
| ID: mdl-35703011
ABSTRACT
Protein signaling complexes play important roles in prevention of several cancer types and can be used for development of targeted therapy. The roles of signaling complexes of phosphodiesterase 3B (PDE3B) and Rap guanine nucleotide exchange factor 3 (RAPGEF3), which are two important enzymes of cyclic adenosine monophosphate (cAMP) metabolism, in cancer have not been fully explored. In the current study, a natural product Kaempferol-3-O-(3'',4''-di-E-p-coumaroyl)-α-L-rhamnopyranoside designated as KOLR was extracted from Cinnamomum pauciflorum Nees leaves. KOLR exhibited higher cytotoxic effects against BxCP-3 pancreatic cancer cell line. In BxPC-3 cells, the KOLR could enhance the formation of RAPGEF 3/ PDE3B protein complex to inhibit the activation of Rap-1 and PI3K-AKT pathway, thereby promoting cell apoptosis and inhibiting cell metastasis. Mutation of RAPGEF3 G557A or low expression of PDE3B inactivated the binding action of KOLR resulting in KOLR resistance. The findings of this study show that PDE3B/RAPGEF3 complex is a potential therapeutic cancer target.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Phosphatidylinositol 3-kinases
/
Cinnamomum
Langue:
En
Journal:
Phytother Res
Sujet du journal:
TERAPIAS COMPLEMENTARES
Année:
2022
Type de document:
Article
Pays d'affiliation:
Chine