Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1

• DOI: 10.1371/journal.pone.0240676
• Publication Date: 2020-10-14T18:31:56Z
• Authors: Sarah Hassan; Jean Peluso; Sandra Chalhoub; Ysia Idoux Gillet; Nadia Benkirane-J...; Natacha Rochel; Guy Fuhrmann; Genevieve Ubeaud-...
• Keywords: Efflux; Hypoxia

The impact of cancer on lifespan is significantly increasing worldwide. Enhanced activity drug efflux pumps and the incidences tumor microenvironment such as apparition a hypoxic gradient inside bulk tumor, are major causes chemotherapy failure. For instance, expression Hypoxia-inducible factor (HIF-1α) has been associated with metastasis, resistance to reduced survival rate. One current challenges fight against therefore find new molecules therapeutic potential that could overcome this chemoresistance. In present study, we focused bioactive plant flavonoid quercetin, which strong antioxidant anti-proliferative properties. We examined efficacy combined treatments quercetin anti-cancer drugs gemcitabine doxorubicin, known specifically act human pancreatic hepatic cells, respectively. Moreover, our study aimed investigate more in-depth implication multidrug transporter MDR1 HIF-1α n chemoresistance if hypoxia-associated effects. observed drugs, were effective when administered in combination shown by an increased percentage dead cells up 60% both 2D 3D cultures. addition, results indicated down-regulated levels regulator apoptosis p53. inhibit MDR1. Finally, vitro suggests efficiency chemotherapeutic might be upon quercetin. This may promising pharmacological agent for novel therapy since it potentializes cytotoxic doxorubicin targeting developed liver