Harnessing Redox Disruption to Treat Human Herpesvirus 8 (HHV-8) Related Malignancies
Adélie Gothland,
Aude Jary,
Philippe Grange,
Valentin Leducq,
Laurianne Beauvais-Remigereau,
Nicolas Dupin,
Anne-Geneviève Marcelin,
Vincent Calvez
Affiliations
Adélie Gothland
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Department of Virology, Hôpital Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
Aude Jary
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Department of Virology, Hôpital Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
Philippe Grange
Cutaneous Biology Lab, INSERM U1016, UMR8104, Institut Cochin, Université de Paris, 24 Rue du Faubourg St Jacques, 75014 Paris, France
Valentin Leducq
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Department of Virology, Hôpital Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
Laurianne Beauvais-Remigereau
SkinDermic, 75003 Paris, France
Nicolas Dupin
Cutaneous Biology Lab, INSERM U1016, UMR8104, Institut Cochin, Université de Paris, 24 Rue du Faubourg St Jacques, 75014 Paris, France
Anne-Geneviève Marcelin
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Department of Virology, Hôpital Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
Vincent Calvez
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Department of Virology, Hôpital Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
Reprogrammed metabolism is regarded as a hallmark of cancer and offers a selective advantage to tumor cells during carcinogenesis. The redox equilibrium is necessary for growth, spread and the antioxidant pathways are boosted following Reactive Oxygen Species (ROS) production to prevent cell damage in tumor cells. Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi sarcoma KS and primary effusion lymphoma (PEL), is an oncogenic virus that disrupts cell survival-related molecular signaling pathways leading to immune host evasion, cells growths, angiogenesis and inflammatory tumor-environment. We recently reported that primaquine diphosphate causes cell death by apoptosis in HHV-8 infected PEL cell lines in vivo and exhibits therapeutic anti-tumor activity in mice models and advanced KS. Our findings also suggest that the primaquine-induced apoptosis in PEL cells is mostly influenced by ROS production and targeting the redox balance could be a new approach to treat HHV-8 related diseases. In this review, we summarized the knowledge about the influence of ROS in cancer development; more specifically, the proof of evidence from our work and from the literature that redox pathways are important for the development of HHV-8 pathologies.
