Background: Carbonic anhydrases (CA), a family of metalloenzymes, play an important role in catalyzing the equilibration of carbon dioxide (CO(2)) and carbonic acid (H(2)CO(3)). The role of CAs in tumorigenesis is controversial, especially regarding the expression of CA isoenzymes between various tumor types. This study explores the correlation between the expressions of CA I and CA II and the characteristic features of oral cancer.
Methods: We immunohistochemically examined the expressions of CA I and CA II in 279 cases of oral squamous cell carcinoma (OSCC) using tissue microarrays. Additionally, the oral cancer cell line SCC-9 was used to confirm the relationship between CA I and CA II expression and cell growth.
Results: We found a significant correlation between positive CA I and CA II stains and OSCC for more advanced clinical stage (P = 0.014 or 0.012) and larger tumor size (P = 0.008 or 0.038), but not for positive lymph node metastasis, distal metastasis, and recurrence. In vitro analysis also showed that treatment with a CA inhibitor, acetazolamide, inhibited the growth of SCC-9 cells.
Conclusion: We conclude that expressions of CA I and CA II in OSCC samples can be used to predict local tumor growth in OSCC patients.
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http://dx.doi.org/10.1111/j.1600-0714.2012.01135.x | DOI Listing |
RSC Med Chem
December 2024
VNU University of Education, Vietnam National University, Hanoi 144 Xuan Thuy, Cau Giay Ha Noi Vietnam.
Some novel sulphonyl thiourea derivatives (7a-m) containing 4,6-diarylpyrimidine rings were designed and synthesized using a one-pot procedure. These compounds exhibited remarkable dual inhibitory activity against human carbonic anhydrase CA I, CA II, CA IX, and XII isoenzymes and some cancer cell lines. Among them, some thioureas had significantly more potent inhibitory activities in the order of 7l > 7c > 7f (against the CA I isoform), 7f > 7b > 7c (against the CA II isoform), 7c > 7g > 7a > 7b (against the CA IX isoform), and 7d > 7c > 7g > 7f (against the CA XII isoform).
View Article and Find Full Text PDFJ Med Chem
January 2025
Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Carbonic anhydrases (CAs) IX and XII are crucial for the survival and metastasis of solid tumors under hypoxic conditions. We designed compounds -, integrating triazole and benzenesulfonamide scaffolds known for inhibiting tumor-associated CAs IX/XII. Initial synthesis included compounds -, followed by diversification with small hydrophobic groups (-) and hydrophilic heterocyclic secondary amines (-).
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Guwahati, India.
This study is focused on the design, synthesis, and evaluation of some sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) enzymes I, II, IX, and XII as well as for their antioxidant activity. The purity of the synthesized molecules was confirmed by the HPLC purity analysis and was found in the range of 93%-100%. The inhibition constant (K) against hCA I ranged from 0.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
NEUROFARBA Department, Section of Pharmaceutical Science, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
The tetrazole group is here proposed as a zinc-binding warhead for the inhibition of the metalloenzyme carbonic anhydrases. A set of synthesized derivatives incorporating the tetrazole moiety were evaluated as inhibitors against a panel of human isoforms, exhibiting values spanning between the submicromolar and low-to-medium micromolar ranges (0.62-19.
View Article and Find Full Text PDFChemMedChem
January 2025
Université de Montpellier, IBMM UMR 5247 - Pôle Chimie Balard Recherche, 1919 Route de Mende, 34293, Montpellier, FRANCE.
Tumor-associated human carbonic anhydrases (hCAs), particularly isoforms hCA IX and hCA XII, are overexpressed in hypoxic regions of solid tumors and play a crucial role in regulating pH homeostasis, promoting cancer cell survival and enhancing invasiveness. These enzymes have emerged as promising therapeutic targets in cancer treatment, including photothermal therapy (PTT). PTT is a minimally invasive technique that uses light-absorbing agents to convert near-infrared (NIR) light into heat, effectively inducing localized hyperthermia and promoting cancer cell apoptosis.
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