Evaluation of the Gene Expression of Hedgehog Signaling Pathway Components in Response to Quinacrine in MDA-MB 231 Cells

Abstract

Background: Hedgehog signaling pathway abnormality plays an important role in the development of various cancers. PTCH1 and SMO proteins are essential receptors in the hedgehog signaling pathway. Quinacrine as a derivative of 9-aminoacridine revealed an inhibitory effect on the growth of some cancer cells. Triple-negative breast cancer with stem cell-like characteristics remains a poor prognostic type. Objectives: In this study, the effect of quinacrine on patched1 protein receptor (PTCH1) and smoothened protein receptor (SMO) gene expression in the hedgehog signaling pathway was evaluated in MDA-MB 231 breast cancer cell line. Methods: Toxicity of quinacrine was determined based on the MTT assay results. MDA-MB 231 breast cancer cells were treated with 0.5 µM quinacrine for 72 hours. The alteration of the hedgehog signaling pathway was studied by quantitative assessment of PTCH1 and SMO gene expression. Results were evaluated using t-test and were analyzed based on P < 0.05. Results: This study showed that 0.5 µM quinacrine decreases SMO gene expression involved in the hedgehog signaling pathway (-2.1 fold) in MDA-MB 231 breast cancer cell line (P = 0.007). Quinacrine had no significant effect on PTCH1 gene expression (P = 0.059). Conclusions: The SMO gene inhibition by quinacrine could affect breast cancer cells growth with respect to its oncogenic role.