Evaluation of the anticancer potential of a sulphonamide carbonic anhydrase IX inhibitor on cervical cancer cells

J Enzyme Inhib Med Chem. 2019 Dec;34(1):703-711. doi: 10.1080/14756366.2019.1579805.

Abstract

Cervical cancer is a common type of cancer. Carbonic anhydrase IX (CA IX) is an attractive target for tumour therapy, being overexpressed in many cancers. We investigated the anticancer properties of the aromatic sulphonamide S-1 as a CA IX inhibitor on cervical cancer cells (HeLa) positive for CA IX expression and normal prostate epithelial cell line (PNT1-A) negative for CA IX. We examined the cytotoxic, apoptosis, genotoxic, and oxidative stress activity of S-1 on HeLa and PNT1-A cell lines. S-1 induced significant reduction of cell viability, caused apoptosis, and up-regulated ROS production. This decrease in cell survival rate can be attributed to the high level of ROS and apoptosis, which has also been shown to arrest the cell cycle. Our findings indicated that S-1 is more effective on HeLa than PNT1-A. S-1 was able to induce apoptosis of cervical cancer cells and is a possible candidate for future anticancer studies.

Keywords: Apoptosis; carbonic anhydrase-IX inhibitor; cervical cancer; cytotoxicity; oxidative stress.

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Reactive Oxygen Species
  • CA9 protein, human
  • Carbonic Anhydrase IX

Grants and funding

This study was supported by the research fund of Van Yuzuncu Yil University (Project No: TYL-2017–5725) and TUBITAK (Project No: 115Z681).