Comparative investigation of Dendrosomal Nano‑Solanine and Solanine in modulating WNT/β‑Catenin and PI3K/AKT/mTOR signaling pathways in HCT116 colorectal cancer cells

Colorectal cancer (CRC) progression is driven by the dysregulation of oncogenic pathways, including Wnt/β-catenin and PI3K/AKT/mTOR pathways. Dendrosomal Nano-Solanine (DNS), a nano-formulation of the glycoalkaloid solanine, may improve bioavailability and potency. This study compares the anticancer effects of DNS versus solanine on key molecular and functional endpoints in HCT116 colorectal cancer cells. To determine gene expression, HCT116 cells were treated with DNS or solanine (4 µg/mL), and the expression levels of Wnt, APC, β-catenin, GSK3β, PI3K, PTEN, AKT , and mTOR genes were assessed by qRT-PCR at 24h and 48h. Protein levels and phosphorylation status were measured by Western blot. Cell viability, proliferation, migration, and apoptosis were examined through MTT assay, wound healing assay, and flow cytometry, respectively, after DNS and solanine treatment. DNS exhibited statistically significantly stronger inhibitory effects at much lower concentrations compared to solanine in both signaling pathways. At this concentration (4 µg/mL), solanine was ineffective or exhibited only negligible effects. DNS statistically significantly upregulated tumor suppressors APC, GSK3β, and PTEN , and downregulated β-catenin, Wnt, PI3K , with reduced phosphorylation of AKT and mTOR at both mRNA and protein levels. Functionally, DNS substantially decreased cell viability, impaired migration by MTT, and wound healing assay. Furthermore, flow cytometry results revealed that DNS treatment was associated with significant cell cycle arrest and promotion of apoptosis in the HCT116 cells. DNS at a lower dose exhibits markedly enhanced anti-tumor activity compared to solanine in HCT116 CRC cells, effectively targeting both Wnt/β-β-catenin and PI3K/AKT/mTOR pathways that are more important in colorectal cancer. These results support its potential as a promising therapeutic agent for CRC, justifying further in vivo and preclinical investigation.