A potentiated cooperation of carbonic anhydrase IX and histone deacetylase inhibitors against cancer.

Abstract

The emergence of tumour recurrence and resistance limits the survival rate for most tumour-bearing patients. Only, combination therapies targeting pathways involved in the induction and in the maintenance of cancer growth and progression might potentially result in an enhanced therapeutic efficacy. Herein, we provided a prospective combination treatment that includes suberoylanilide hydroxamic acid (SAHA), a well-known inhibitor of histone deacetylases (HDACs), and SLC-0111, a novel inhibitor of carbonic anhydrase (CA) IX. We proved that HDAC inhibition with SAHA in combination with SLC-0111 affects cell viability and colony forming capability to greater extent than either treatment alone of breast, colorectal and melanoma cancer cells. At the molecular level, this therapeutic regimen resulted in a synergistically increase of histone H4 and p53 acetylation in all tested cell lines. Overall, our findings showed that SAHA and SLC-0111 can be regarded as very attractive combination providing a potential therapeutic strategy against different cancer models.

• Authors: Jessica Ruzzolini, Anna Laurenzana, Elena Andreucci, Silvia Peppicelli, Francesca Bianchini, Fabrizio Carta, Claudiu T Supuran, Maria Novella Romanelli, Chiara Nediani, Lido Calorini
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 35 Issue 1 Pg. 391-397 (Dec 2020) ISSN: 1475-6374 [Electronic] England
• PMID: 31865754 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Carbonic Anhydrase Inhibitors
• Histone Deacetylase Inhibitors
• Phenylurea Compounds
• SLC-0111
• Sulfonamides
• Histone Deacetylases
• CA9 protein, human
• Carbonic Anhydrase IX

Topics

• Antigens, Neoplasm (metabolism)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carbonic Anhydrase IX (antagonists & inhibitors, metabolism)
• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Histone Deacetylase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Histone Deacetylases (metabolism)
• Humans
• Molecular Structure
• Phenylurea Compounds (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Sulfonamides (chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured