Quercetin alters redox homeostasis, induces MAPK activation and promotes DNA damage in vGPCR-transformed endothelial cells

Quercetin (QUE), a naturally occurring flavonoid, has been shown to reduce cell viability and proliferation in vGPCR-transformed endothelial cells, cells associated with Kaposi's sarcoma. This study delves into the mechanisms behind QUE's antineoplastic effects on these cells, an in vitro model of Kaposi's sarcoma. Initially, QUE activated MAPK signaling pathways in vGPCR cells, elevating the phosphorylation levels of ERK1/2, JNK1/2, and p38, without influencing AKT phosphorylation.

Concurrently, QUE increased intracellular oxidant levels, subsequently leading to lipid peroxidation and DNA damage. This observation underscores the connection between oxidative imbalance and genotoxicity. Nevertheless, an increased total glutathione content, alongside unaltered Gpx4 mRNA expression, suggests the induction of oxidative stress and compensatory antioxidant responses.

Notably, elevated intracellular oxidant levels correlate with MAPK signaling activation, especially JNK1/2, while ERK1/2 and p38 activation might indicate a compensatory response that falls short of overcoming QUE-induced cytotoxicity. In summary, these findings reveal that QUE exhibits antiproliferative effects in vGPCR cells through oxidative stress, MAPK activation, and DNA damage, suggesting its potential significance in exploring therapeutic approaches for virus-associated malignancies.