2. Academic Validation
  3. The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy

The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy

  • J Enzyme Inhib Med Chem. 2019 Dec;34(1):117-123. doi: 10.1080/14756366.2018.1532419.
Elena Andreucci 1,  Jessica Ruzzolini 1,  Silvia Peppicelli 1,  Francesca Bianchini 1,  Anna Laurenzana 1,  Fabrizio Carta 2,  Claudiu T Supuran 2,  Lido Calorini 1 3
Affiliations

Affiliations

  • 1 a Department of Clinical and Experimental Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology , University of Florence , Florence , Italy.
  • 2 b Department of NEUROFARBA , University of Florence , Florence , Italy.
  • 3 c Center of Excellence for Research, Transfer and High Education DenoTHE , University of Florence , Florence , Italy.
PMID: 30362384 DOI: 10.1080/14756366.2018.1532419
Abstract

Drug combination represents one of the most accredited strategies of Cancer therapy able to improve drug efficacy and possibly overcome drug resistance. Among the agents used to complement conventional chemotherapy, Carbonic Anhydrase IX (CAIX) inhibitors appear as one of the most suitable, as markers of hypoxic and acidic Cancer cells which do not respond to chemo- and radiotherapy. We performed preclinical in vitro assays to evaluate whether the SLC-0111 CAIX inhibitor co-operates and potentiates the cytotoxic effects of conventional chemotherapeutic drugs in A375-M6 melanoma cells, MCF7 breast Cancer cells, and HCT116 colorectal Cancer cells. Here, we demonstrate that the SLC-0111 CAIX inhibitor potentiates cytotoxicity of Dacarbazine and Temozolomide currently used for advanced melanoma treatment. SLC-0111 also increases breast Cancer cell response to Doxorubicin and enhances 5-Fluorouracil cytostatic activity on colon Cancer cells. These findings disclose the possibility to extend the use of CAIX inhibitors in the combination therapy of various Cancer histotypes.

Keywords

CAIX inhibitor; Chemotherapy; SLC-0111; combined therapy; drug resistance.

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