ArticleAntioxidants & redox signaling2013
A role for virally induced reactive oxygen species in Kaposi's sarcoma herpesvirus tumorigenesis.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- Latency-Associated Nuclear Antigen (LANA) Promotes Ferroptosis by Suppressing Nrf2/GPX4 and Upregulating MDM2.Pathogens (Basel, Switzerland) · 2025Article
- Rho-GTPases subfamily: cellular defectors orchestrating viral infection.Cellular & molecular biology letters · 2025Review
- In Vitro Studies of Pegylated Magnetite Nanoparticles in a Cellular Model of Viral Oncogenesis: Initial Studies to Evaluate Their Potential as a Future Theranostic Tool.Pharmaceutics · 2023Article
- A major role for Nrf2 transcription factors in cell transformation by KSHV encoded oncogenes.Frontiers in oncology · 2022Article
- Metabolic landscapes in sarcomas.Journal of hematology & oncology · 2021Review
- The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.The British journal of nutrition · 2021Article
- Targeting the signaling in Epstein-Barr virus-associated diseases: mechanism, regulation, and clinical study.Signal transduction and targeted therapy · 2021Review
- A Non-Coding RNA Network Involved in KSHV Tumorigenesis.Frontiers in oncology · 2021Article
- Identification of Mubritinib (TAK 165) as an inhibitor of KSHV driven primary effusion lymphoma via disruption of mitochondrial OXPHOS metabolism.Oncotarget · 2020Article
- KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma.PLoS pathogens · 2020Article
- Article
- Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation.PLoS pathogens · 2020Article
- High-throughput sequencing analysis of a "hit and run" cell and animal model of KSHV tumorigenesis.PLoS pathogens · 2020Article
- Human Herpesvirus 8 and Host-Cell Interaction: Long-Lasting Physiological Modifications, Inflammation and Related Chronic Diseases.Microorganisms · 2020Review
- Human Herpesvirus 8 infection may contribute to oxidative stress in diabetes type 2 patients.BMC research notes · 2020Article
- Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.Theranostics · 2020Article
- Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3.Journal of virology · 2019Article
- HACE1, an E3 Ubiquitin Protein Ligase, Mitigates Kaposi's Sarcoma-Associated Herpesvirus Infection-Induced Oxidative Stress by Promoting Nrf2 Activity.Journal of virology · 2019Article
- Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.Frontiers in microbiology · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aimsKaposi's sarcoma (KS), caused by the Kaposi's sarcoma herpesvirus (KSHV), is an AIDS-associated cancer characterized by angiogenesis and proliferation of spindle cells. Rac1-activated reactive oxygen species (ROS) production has been implicated in KS tumorigenesis. We used an animal model of KSHV-induced Kaposi's sarcomagenesis (mECK36) to study the role of ROS in KS and the efficacy of N-acetyl l-cysteine (NAC) in inhibiting or preventing KS.
resultsSignaling by the KSHV early lytic gene viral G protein-coupled receptor (vGPCR) activated ROS production in mECK36 cells via a Rac1-NADPH oxidase pathway. Induction of the lytic cycle in KSHV-infected KS spindle cells upregulated ROS along with upregulation of vGPCR expression. We also found that expression of the major latent transcript in 293 cells increased ROS levels. ROS scavenging with NAC halted mECK36 tumor growth in a KSHV-specific manner. NAC inhibited KSHV latent gene expression as well as tumor angiogenesis and lymphangiogenesis. These effects correlated with the reduction of vascular endothelial growth factor (VEGF), c-myc, and cyclin D1, and could be explained on the basis of inhibition of STAT3 tyrosine phosphorylation. NAC prevented mECK36 de novo tumor formation. Molecular analysis of NAC-resistant tumors revealed a strong upregulation of Rac1 and p40(PHOX). INNOVATION AND
conclusionOur results demonstrate that ROS-induction by KSHV plays a causal role in KS oncogenesis by promoting proliferation and angiogenesis. Our results show that both ROS and their molecular sources can be targeted therapeutically using NAC or other Food and Drug Administration (FDA)-approved inhibitors for prevention and treatment of AIDS-KS.
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