Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Abstract

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

• Authors: Fabrizio Angius, Enrica Piras, Sabrina Uda, Clelia Madeddu, Roberto Serpe, Rachele Bigi, Wuguo Chen, Dirk P Dittmer, Raffaello Pompei, Angela Ingianni
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 70 Issue 9 Pg. 962-966 (Aug 2017) ISSN: 1881-1469 [Electronic] England
• PMID: 28611469 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antigens, Viral
• Antiviral Agents
• DNA, Viral
• Nuclear Proteins
• Recombinant Fusion Proteins
• Sulfanilamides
• Sulfathiazoles
• Sulfonamides
• TP53 protein, human
• Tumor Suppressor Protein p53
• latency-associated nuclear antigen
• Sulfaguanidine
• Sulfanilamide
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2
• Sulfamethoxazole
• Sulfathiazole

Topics

• Anti-Bacterial Agents (adverse effects, pharmacology)
• Antigens, Viral (metabolism)
• Antiviral Agents (adverse effects, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Cell Transformation, Viral (drug effects)
• Cells, Cultured
• DNA, Viral (metabolism)
• Herpesvirus 8, Human (drug effects, growth & development, metabolism)
• Human Umbilical Vein Endothelial Cells (cytology, drug effects, metabolism, virology)
• Humans
• Inhibitory Concentration 50
• Nuclear Proteins (metabolism)
• Protein Multimerization (drug effects)
• Proto-Oncogene Proteins c-mdm2 (antagonists & inhibitors, chemistry, genetics, metabolism)
• Recombinant Fusion Proteins (chemistry, metabolism)
• Sulfaguanidine (adverse effects, pharmacology)
• Sulfamethoxazole (adverse effects, pharmacology)
• Sulfanilamide
• Sulfanilamides (adverse effects, pharmacology)
• Sulfathiazole
• Sulfathiazoles (adverse effects, pharmacology)
• Sulfonamides (adverse effects, pharmacology)
• Tumor Suppressor Protein p53 (antagonists & inhibitors, chemistry, genetics, metabolism)