The effect of dendrosomal nanocurcumin on Wnt/β-catenin signaling pathway via PIWIL2 in MCF-7 breast cancer cells

Abstract

Breast cancer ranks as one of the most prevalent cancers impacting women worldwide, posing significant treatment challenges due to chemotherapy resistance and high recurrence rates. This study investigates the therapeutic potential of Dendrosomal Nanocurcumin (DNC), a novel formulation aimed at enhancing curcumin's bioavailability. The focus is on its impact on the Wnt/β-catenin signaling pathway via the modulation of the PIWIL2 protein in MCF-7 breast cancer cells.The Wnt/β-catenin signaling pathway is crucial for controlling cell proliferation, differentiation, and apoptosis. Its dysregulation is strongly linked to breast cancer progression. PIWIL2, a member of the PIWI subfamily of Argonaute proteins, plays a role in RNA silencing, DNA methylation, histone modification, gene transcription regulation, and interactions with oncogenic pathways. These functions highlight its importance in gene regulation, stem cell maintenance, and cancer progression.In this study, MCF-7 cells were treated with Dendrosomal Nanocurcumin at a dose of 20µM for 48 h, based on the IC50 determined from the MTT assay. Real-time PCR analysis revealed that DNC treatment significantly reduced the expression levels of β-catenin (p < 0.0001), Cyclin D1 (p < 0.0001), and PIWIL2 (p < 0.00001), while significantly increasing the expression of GSK3β (p < 0.0001).These findings were supported by Western blot analysis, which showed a significant decline in both phosphorylated and non-phosphorylated forms of β-catenin and PIWIL2 proteins. This suggests that DNC disrupts the Wnt/β-catenin signaling pathway by reducing the stability and cytoplasmic accumulation of β-catenin. The reduction in β-catenin likely prevents its nuclear translocation and the subsequent activation of target genes like Cyclin D1, thus inhibiting cell proliferation and promoting apoptosis. Furthermore, a significant decrease in PIWIL2 protein levels in DNC-treated cells indicates that DNC targets PIWIL2, further inhibiting the Wnt/β-catenin signaling pathway and reducing the oncogenic potential of MCF-7 breast cancer cells.These findings highlight the potential of DNC as an effective treatment option for breast cancer, particularly in overcoming resistance to conventional therapies. Further research is necessary to gain a comprehensive understanding the mechanisms of DNC and its clinical efficacy, offering hope for enhanced breast cancer treatment strategies.

Keywords: Curcumin; DNC; MCF-7; PIWIL2; Wnt/β-catenin signaling.