Therapeutic Effects of Taraxasterol on Triple-Negative Breast Cancer (MDA-MB-231 Cells) Through Modulation of the Novel AKT/mTOR/β-Catenin Signaling Pathway

Abstract

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) with high resistance to chemotherapy. Taraxasterol is isolated from Taraxacum officinale (TO) with anti-cancer effects. Objectives: The present study aimed to investigate the anticancer effect of taraxasterol on TNBC cells. Methods: Taraxacum officinale extract was prepared and purified with concentrations ranging from 1 to 128 μM. MDA-MB-231 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and treated with TO for 24 to 96 hours. Cell viability was assessed using the MTT assay, and apoptosis was evaluated by the diphenylamine method. Gene expression of HPRT, OPN, AKT1, mTOR, PTEN, and β-Catenin was measured by real-time PCR using the 2-ΔΔCt method on the StepOne system. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test in SPSS, with significance set at P < 0.05. Results: After 24, 48, 72, and 96 h of treatment with taraxasterol, cell viability was decreased (P < 0.05). The IC50 values were respectively found 439.37 ± 6.8, 213.27 ± 5.78, 121 ± 7.98 and 27.86 ± 9.66 μM following 24, 48, 72, and 96 h of taraxasterol exposure. Diphenylamine assay showed that IC50 concentration of taraxasterol causes a significant increase in apoptosis after 24 h. Also, after 24 h of treatment, taroxasterol induced a significant decrease in gene expression of HPRT, OPN, AKT1, mTOR, and β-Catenin. Conclusions: Taraxasterol can reduce survival rate and induce apoptosis in TNBC cells through disruption of the AKT/mTOR/β-Catenin pathway.