Pharmacological Inhibition Of P300 Exerts An Antitumor Role In Thyroid Cancer

Abstract

Thyroid Cancer (TC) is the most prevalent endocrine tumor worldwide. p300 is a protein that functions as a transcriptional cofactor, histone acetyltransferase, and lysine acetyltransferase for proteins involved in functions other than transcription. A relationship of p300 with cancer has been demonstrated, however, its role is still unclear since it has been documented as a tumor suppressor and/or as an oncoprotein. In our laboratory, we have established an association between p300 and breast cancer, observing a protumoral role. Due to the limited studies on p300 and TC, it is interesting to investigate p300 expression and the cellular and molecular mechanisms through which this protein could be involved in tumor progression of TC. The objective of this work was to study the effect of inhibiting the acetylase function of p300 on the processes of apoptosis and metastasis in human TC cells. The treatment of human papillary TC cell line, TPC-1, with VV59 (inhibitor of p300 acetylase function) or its vehicle (DMSO) produced a decrease in the number of cells compared to the vehicle (crystal violet assay and manual counting, p<0.0001). When we analyzed the cell cycle by flow cytometry, we detected an increase in the sub G0/G1 phase and a decrease in the G0/G1 phase in cells treated with VV59 compared to those treated with the vehicle (p<0.001). In addition, we detected a decrease in p53 protein expression (Western Blot) and an increase in the cytoplasmic levels of p53 and p300 (immunofluorescence) in cells treated with VV59 compared to cells treated with vehicle. On the other hand, we detected that pharmacological inhibition of p300 decreases cell migration (wound healing assay, p<0.0001), invasion (matrigel assay, p<0.0001), and cell adhesion (crystal violet assay, p<0.0001). Taken together, these results demonstrate an antitumoral role for the pharmacological inhibition of p300 acetylase function in the human TC cell line.