31
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Nutlin-3 induces apoptosis, disrupts viral latency and inhibits expression of angiopoietin-2 in Kaposi sarcoma tumor cells.

      Cell Cycle
      Angiopoietin-2, biosynthesis, Animals, Apoptosis, drug effects, Cell Line, Tumor, Cell Proliferation, G1 Phase Cell Cycle Checkpoints, Herpesvirus 8, Human, physiology, Human Umbilical Vein Endothelial Cells, metabolism, Humans, Imidazoles, pharmacology, Mice, Mice, Nude, Piperazines, Proto-Oncogene Proteins c-mdm2, antagonists & inhibitors, Sarcoma, Kaposi, pathology, virology, Telomerase, Tumor Suppressor Protein p53, genetics, Virus Latency, Xenograft Model Antitumor Assays

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Kaposi sarcoma (KS) tumors often contain a wild-type p53. However, the function of this tumor suppressor in KS tumor cells is inhibited by both MDM2 and latent nuclear antigen (LANA) of Kaposi sarcoma-associated herpes virus (KSHV). Here, we report that MDM2 antagonist Nutlin-3 efficiently reactivates p53 in telomerase-immortalized human umbilical vein endothelial cells (TIVE) that had been malignantly transformed by KSHV as well as in KS tumor cells. Reactivation of p53 results in a G 1 cell cycle arrest, leading to inhibition of proliferation and apoptosis. Nutlin-3 inhibits the growth of "KS-like" tumors resulting from xenografted TIVE-KSHV cells in nude mice. In addition, Nutlin-3 strongly inhibits expression of the pro-angiogenic and pro-inflammatory cytokine angiopoietin-2 (Ang-2). It also disrupts viral latency by inducing expression of KSHV lytic genes. These results suggest that Nutlin-3 might serve as a novel therapy for KS.

          Related collections

          Author and article information

          Comments

          Comment on this article