Caffeic acid phenethyl ester suppresses the expression of androgen receptor variant 7 via inhibition of CDK1 and AKT.
Cancer Gene Ther
; 31(6): 807-815, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38480977
ABSTRACT
Androgen receptor (AR) splice variant 7 (AR-V7) is capable to enter nucleus and activate downstream signaling without ligand. AR-V7 assists the tumor growth, cancer metastasis, cancer stemness, and the evolvement of therapy-resistant prostate cancer (PCa). We discovered that caffeic acid phenethyl ester (CAPE) can repress the expression and downstream signaling of AR-V7 in PCa cells. CAPE blocked the gene transcription, nuclear localization, and protein abundance of AR-V7. CAPE inhibited the expression of U2AF65, SF2 and hnRNPF, which were splicing factors for AR-V7 intron. Additionally, CAPE decreased protein stability of AR-V7 and enhanced the proteosome-degradation of AR-V7. We observed that CDK1 and AKT regulated the expression and stability of AR-V7 via phosphorylation of Ser81 and Ser213, respectively. CAPE decreased the expression of CDK1 and AKT. Overexpression of CDK1 restored the abundance of AR-V7 in CAPE-treated PCa cells. Overexpression of AR-V7, AKT or CDK1 rescued the proliferation of PCa cells under CAPE treatment. Intraperitoneal injection of 10 mg/kg CAPE retarded the growth of 22Rv1 xenografts in nude mice and suppressed the protein levels of AR-V7, CDK1 and AKT in 22Rv1 xenografts. Our study provided the rationale of applying CAPE for inhibition of AR-V7 in prostate tumors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylethyl Alcohol
/
Prostatic Neoplasms
/
Caffeic Acids
/
Receptors, Androgen
/
CDC2 Protein Kinase
/
Proto-Oncogene Proteins c-akt
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cancer Gene Ther
Journal subject:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2024
Document type:
Article
Affiliation country:
Taiwán
Country of publication:
Reino Unido