The effect of colon cancer cell line carbonic anhydrase ix inhibition on the gene of EZH2 and histone 3 modifications

Colorectal cancer is one of the most common gastrointestinal cancers with high mortality and morbidity rates. Various genetic and molecular changes occur with the malign transformation of these cancers. For example, Genomic histone modifications such as Abnormal methylated genes, DNA abnormalities, cpg islands methylation may occur. Tumour cells modify themselves in order to adapt the changes in their micro environment. It is well known that many physiological events are catalysed by carbonic anhydrase enzyme family (CA, EC 4.2.1.1) such as CO2/bicarbonate transport, homeostasis, tumour formation which are the common points of tumours. Because the expression of Tumour related CA IX enzyme which was used in this study is related with different type of cancers and induced by hypoxic environment, it is thought to be marker of prognosis. The aim of this study is investigating the effect of Inhibition of Tumour Related Carbonic Anhydrase IX at Colon Cancer HT 29 Cell Line on CO2/HCO3- buffer system H+ ion concentration and epigenetic modifications. In this study it was found that the Inhibition of CA IX caused decrease in and related with that decrease in HIF1α expression acidification (p<0.01). In conjunction with increase in EZH2 gene expression(p<0.05) seems to be also important. The increase in methylation of HT-29 Histone 3 after the inhibition of CA IX enzyme under normoxic conditions seems to induce a reduction of histone methylation in hypoxic conditions. Additionally (Moreover), inhibition of CA IX enzyme induces the increase in acetylation under normoxic conditions while it decreases the acetylation under hypoxic conditions.