Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO 2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of benzothiazole-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I and hCA II and the transmembrane hCA IX and hCA XII. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting hCA IX and hCA XII over the off-target ones hCA I and hCA II. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.
Head and neck cancer (HNC) is one of the most common malignancies in the world. HNC is a group of cancers that starts in the mouth, nose, throat, larynx, sinuses, or salivary glands. According to this section of the body parts; induction of cancer can be associated with CO2 and oxidative stress. The aim of this study is to assess the activities of carbonic anhydrase (CA), catalase (CAT), paraoxonase1 (PON1), and xanthine oxidase (XO) activities in 89 HNC patients and 115 healthy volunteers. Paraoxonase1 activity was found lower in HNC cancer patients. There is no statistically significant difference between patients and controls for catalase, carbonic anhydrase, and xanthine oxidase enzyme levels. According to this results, paraoxonase1 levels could be a candidate as an oxidative marker in HNC patients, but further studies are needed to investigate the other type of cancer related PON1 and the other enzyme levels.
Objectives
To determine the effects of hypoxia-inducible factors (HIF)-1 inhibitors on carbonic anhydrase-IX (CA-IX) enzyme and vascular endothelial growth factor (VEGF) in melanoma. The HIF-1 pathway induces tumor growth and metastasis by stimulating the expression of CA-IX enzyme and VEGF proteins.
Methods
We evaluated the inhibition effects of Acriflavine and Echinomycin on CA-IX enzyme and VEGF in WM115 (primary) and SKMEL30 (metastatic) cell lines in normoxic and hypoxic conditions with Enzyme Linked Immunosorbent Assay. The cytotoxic activity of HIF-1 inhibitors was performed by using WST-1 assay. All experiments were performed at 450 nm using Epoch™ Microplate Spectrophotometer.
Results
IC50 values were observed with a concentration of 3 μmol/L for Echinomycin and Acriflavine in the WST-1 assay. Decreased CA-IX and VEGF levels were determined in both normoxia and hypoxia after inhibitors’ treatment with WM115 and SKMEL30 cell lines (p<0.05). Inhibitory effect of HIF-1 inhibitors on CA-IX and VEGF proteins was observed in cell lines WM115 and SKMEL30.
Conclusions
Due to the importance of our study, using HIF-1 inhibitors may be an alternative treatment for melanoma. Also to design new HIF-1 inhibitor derivatives is a promising approach for further studies targeting CA-IX enzyme and VEGF.
Oksidatif stres, renal kanser için önemli parametrelerden birisidir. Antioksidan sistem renal kanser oluşumunda devreye girerek oksidatif strese karşı koyar. Endojen antioksidanlar olarak tanımlanan GR ve GPx, böbreklerin antioksidan sistemindeki önemli enzimleridir. Çalışmamızın temel amacı, bir karbonik anhidraz enzim inhibitörü olan AZA’nın glutatyon mekanizması üzerine olan etkisinin renal kanserde incelenmesidir. Deneysel çalışmalarda öncelikle renal kanser hücre hattı olan CAKI-2 çoğaltılarak WST-1 sitotoksisite testi ile AZA’nın uygun dozu 48. saatte 8.65 µM olarak bulunmuştur. CAKI-2 hücrelerine AZA uygulandıktan sonra GR ve GPx üzerine olan etkisinin belirlenmesi için “Glutathione Reductase Assay Kit” ve “Glutathione Peroxidase Assay Kit” kullanılarak Epoch™ Microplate Spectrophotometer cihazında 340 nm’de ölçüm yapılmıştır. AZA uygulaması sonrası GR ve GPx enzim aktivitelerinde artış görülmüştür (p
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