Exploring the role of quercetin on doxorubicin and lapatinib-mediated cellular and mitochondrial responses using in vitro and in silico studies.

Abstract

Doxorubicin (DOX) and lapatinib (LAP) have been reported to cause liver toxicity. The roles of mitochondrial and cellular responses in DOX and LAP mediated-hepatotoxicity have not been investigated with or without quercetin (QUE) in HepG2 cells sensitive to mitochondrial damage (high-glucose or galactose media) in addition to in silico studies. Our results revealed that cytosolic pathways might play role a in DOX-induced cytotoxicity rather than mitochondria. QUE exacerbated DOX-induced ATP depletion in both environments. Our data also indicated that cytosolic and mitochondrial pathways might play a role in LAP-induced cytotoxicity. Incubating QUE with LAP increased ATP levels in high-glucose media. Therefore, QUE might have protective effect against LAP-induced cytotoxicity resulting from cytosolic pathways. The findings from in vitro experiments that QUE increased DOX or LAP-induced mitochondrial dysfunction were confirmed by the results from in silico studies indicating that QUE incubated with LAP or DOX might increase mitochondrial dysfunction.