Abstract
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein required in the DNA base excision repair pathway and a noteworthy reducing-oxidizing factor that regulates the activity of various transcription factors. Cyclin-dependent kinases (CDKs) assume a key role in directing the progression of the cell- cycle. The present study evaluated the synergistic efficacy of using licochalcone B (LCB) and fullerene C(60) (FnC(60)) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma in rats and relevant signaling pathways, with APE1/Ref-1 and CDK-4, as novel anti-cancer- targeting. LCB alone and in combination with FnC(60) significantly decreased DNA fragmentation, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine levels), APE1/Ref-1, CDK-4, retinoblastoma, B- cell lymphoma-2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL), and β-arrestin-2 mRNA expression, and APE1/Ref-1 and CDK-4 protein expression. In contrast, these treatments significantly increased the expression of protein 53 (p53), Bcl-2-associated X protein (Bax), and caspase-3. These data suggest that LCB either alone or in combination with FnC(60) elicited significant protective effects against DEN-induced hepatocarcinogenesis, which may have occurred because of the regulation of enzymes involved in DNA repair and cell-cycle control at S phase progression as well as the induction of apoptosis at the gene and protein expression levels. Furthermore, FnC(60) potentiated the effect of LCB at the molecular level, possibly through targeting of cancerous cells.