Sdy-1 Executes Antitumor Activity in HepG2 and HeLa Cancer Cells by Inhibiting the Wnt/ß-Catenin Signaling Pathway.
Mar Drugs
; 20(2)2022 Feb 05.
Article
in En
| MEDLINE
| ID: mdl-35200654
ABSTRACT
Demethylincisterol A3 (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/ß-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on ß-catenin to reduce its transcription level, thereby reducing the level of ß-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and ß-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sterols
/
Uterine Cervical Neoplasms
/
Carcinoma, Hepatocellular
/
Liver Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Mar Drugs
Journal subject:
BIOLOGIA
/
FARMACOLOGIA
Year:
2022
Type:
Article
Affiliation country:
China