Mitotic spindle defects and DNA damage induced by dimethoxycurcumin lead to an intrinsic apoptosis pathway in HepG2/C3A cells.

Mitotic spindle defects and DNA damage induced by dimethoxycurcumin lead to an intrinsic apoptosis pathway in HepG2/C3A cells. Toxicol In Vitro. 2019 Sep 09;:104643 Authors: Zanetti TA, Biazi BI, Coatti GC, Baranoski A, Marques LA, Corveloni AC, Mantovani MS Abstract Dimethoxycurcumin (DiMC), a synthetic analog of curcumin, was shown to have antiproliferative activity in human tumor cell lines. Therefore, we investigated its cytotoxic, antiproliferative, genotoxic, and apoptotic effect and correlated these evaluations with the expression of transcripts and proteins in the human hepatocellular carcinoma cell line (HepG2/C3A). Treatment with DiMC resulted in increased CYP2E1, CYP2C19 and CYP1A2 transcripts levels and was cytotoxic (≥10 μM). DiMC caused mitotic arrest by inducing monopolar spindle formation and was genotoxic increasing expression of the CDKN1A, GADD45A and PARP1 gene, key effectors in the cell cycle arrest and DNA repair pathways, respectively. This genotoxicity was caused by generation of reactive oxygen species and reduction of antioxidant proteins levels. Furthermore, we observed a decrease in important proteins involved in DNA repair. In addition to the observed apoptotic morphology and the presence of annexin labeling, we observed increased expression of BAK1 and CASP7 genes and caspase 3/7 protein activity, showing that these effects caused apoptosis through the intrinsic pathway in HepG2/C3A cells. Our resul...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research