Quercetin Interrupts the Positive Feedback Loop Between STAT3 and IL-6, Promotes Autophagy, and Reduces ROS, Preventing EBV-Driven B Cell Immortalization
Marisa Granato,
Maria Saveria Gilardini Montani,
Claudia Zompetta,
Roberta Santarelli,
Roberta Gonnella,
Maria Anele Romeo,
Gabriella D’Orazi,
Alberto Faggioni,
Mara Cirone
Affiliations
Marisa Granato
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Maria Saveria Gilardini Montani
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Claudia Zompetta
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Roberta Santarelli
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Roberta Gonnella
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Maria Anele Romeo
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Gabriella D’Orazi
Translational Research Area, Regina Elena National Cancer Institute, 00128 Rome, Italy
Alberto Faggioni
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
Mara Cirone
Department of Experimental Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy
The oncogenic gammaherpesvirus Epstein−Barr virus (EBV) immortalizes in vitro B lymphocytes into lymphoblastoid cell lines (LCLs), a model that gives the opportunity to explore the molecular mechanisms driving viral tumorigenesis. In this study, we addressed the potential of quercetin, a widely distributed flavonoid displaying antioxidant, anti-inflammatory, and anti-cancer properties, in preventing EBV-driven B cell immortalization. The results obtained indicated that quercetin inhibited thectivation of signal transducer and activator of transcription 3 (STAT3) induced by EBV infection and reduced molecules such as interleukin-6 (IL-6) and reactive oxidative species (ROS) known to be essential for the immortalization process. Moreover, we found that quercetin promoted autophagy and counteracted the accumulation of sequestosome1/p62 (SQSTM1/p62), ultimately leading to the prevention of B cell immortalization. These findings suggest that quercetin may have the potential to be used to counteract EBV-driven lymphomagenesis, especially if its stability is improved.
