Document Type

Article

Publication Date

12-31-2018

Publication Title

Journal of Cancer

Abstract

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA damage, reducing the levels of intracellular iron and reactive oxygen species (ROS) and increasing viral lytic gene expression. By using a KS-like nude mouse model, we found that 3-AP treatment significantly suppressed KSHV induced tumorigenesis . Taken together, our data demonstrate targeting RR by 3-AP may represent a promising strategy for improving the treatment of KS in future.

First Page

4503

Last Page

4509

PubMed ID

30519356

Volume

9

Issue

23

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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