Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.
Cancer Chemother Pharmacol
; 93(5): 411-425, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38191768
ABSTRACT
BACKGROUND:
Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies.METHODS:
To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties.RESULTS:
Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation.CONCLUSIONS:
Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.Key words
Full text:
1
Collection:
01-internacional
Health context:
1_ASSA2030
/
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Apoptosis
/
Colonic Neoplasms
/
Artemisinins
/
G1 Phase Cell Cycle Checkpoints
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Chemother Pharmacol
Year:
2024
Document type:
Article