Overview of the Large DNA Tumor Viruses

Verma, Subhash C.; Cai, Qiliang; Bajaj, Bharat; Robertson, Erle S.

doi:10.1007/978-0-387-68945-6_8

Cited by 1 publication

(1 citation statement)

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“…EBV and KSHV have evolved strategies to promote cell survival while protecting infected cells from apoptosis. Infections induce widespread genetic and proteomic responses in the host cell (Verma et al., 2009). While certain cancers have strict viral associations, most clinical therapies used to treat these malignancies do not specifically target oncogenic viral mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Small molecule growth inhibitors of human oncogenic gammaherpesvirus infected B‐cells

Dzeng

Jha

et al. 2014

Molecular Oncology

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Epstein-Barr virus (EBV) and Kaposi’s sarcoma associated herpesvirus (KSHV) are two human gammaherpesviruses associated with a broad spectrum of B-cell lymphomas, most acutely in immuno-compromised populations. However, there are no drugs which specifically target KSHV or EBV-associated lymphomas. To identify small molecules which selectively inhibit the growth of EBV or KSHV-associated B-cell lines, we performed a fluorescence based high-throughput screen on multiple stable GFP expressing virus-infected or uninfected B-cell lines. We identified 40 initial compounds with selective growth inhibition and subsequently determined the 50% growth inhibitory concentrations (GI50) for each drug. We further examined compounds with higher specificity to explore the underlying molecular mechanisms using transcription factor analysis, as well as a sh-RNA based knockdown strategy. Our data identified ten compounds with relatively high efficacy for growth inhibition. Two novel small molecules, NSC#10010 and NSC#65381 were potent growth inhibitors for gammaherpesvirus-associated B-lymphomas through activation of both the NF-κB and c-Myc- mediated signaling pathways. These drugs can serve as potential lead compounds to expand the current therapeutic window against EBV or KSHV associated human B-cell malignancies.

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Section: Introductionmentioning

confidence: 99%