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.

Objective: The Hippo signaling pathway has important role in the pathogenesis of some tumors. Breast cancer is the most prevalent cancer among females in the world. In recent years, various articles referred to inhibiting effect of quinacrine, a derivative of 9-aminoacridine, on the growth of several types of cancer cells. In this study, we evaluated the effect of quinacrine on expression of LATS1, LATS2, and YAP genes of the Hippo signaling pathway and YAP level in human breast cancer stem cells (MDA-MB 231 cell line). This cell line of breast cancer expresses the triple negative characteristics. Methods: MDA-MB 231 cells was treated with 0.5 µM of quinacrine for 3 days. The dose was selected using MTT assays. The expression of genes was quantified by Real-time PCR. The protein expression was performed by Western blotting. Significance of observations were checked by means of Mann-Whitney test using p<0.05 as the level of significance. Results: The present study demonstrated that expression of YAP gene in MDA-MB 231 cell line significantly down regulated by quinacrine. Quinacrine significantly decreased the amount of YAP protein. Moreover, quinacrine did not have meaningful effect on LATS1 and LATS2 genes expression. Conclusion: YAP gene is an oncogene and inhibition of its expression by quinacrine could effect on breast cancer cell progression.