Abstract
BACKGROUND: Breast cancer is the second leading cause of cancer deaths among women. Recent studies emphasize the significant role of folate metabolic pathways in cancer progression. The Reduced Folate Carrier (RFC), a folate transporter in cell membranes, plays an essential role in transporting folate receptor-dependent drugs. Curcumin, a bioactive compound with anticancer and anti-inflammatory effects, is hindered by low stability and a short half-life. Niosomes are versatile nanoparticles that can deliver both hydrophilic and hydrophobic drugs. OBJECTIVE: This study aims to evaluate the anticancer effects of curcumin-loaded niosomal nanoparticles, focusing on their impact on RFC, BAX, and BCL-2 gene expression in MDA-MB-231 breast cancer cells. METHODS: Curcumin-loaded noisomal nanoparticles were synthesized by the thin-film hydration method. Then, the morphology, size, and physico-chemical nanoparticles were determined by FE-SEM, DLS, and FT-IR methods, respectively. The MTT results determined the cytotoxicity of free and nano-formulated curcumin; also, the gene expression of RFC, BCL-2, and BAX was evaluated using the Real-Time PCR method. Furthermore, apoptosis and cell cycle analysis were investigated by Flow cytometry. Results: The results of the physicochemical characteristics of the nanoparticles showed that curcumin was appropriately loaded in niosomal NPs. The MTT results showed that curcumin loaded in niosomal NPs has a higher anti-proliferative effect than free curcumin. Real-time PCR results showed increased RFC and BAX gene expression and decreased BCL-2 gene expression; this change was more significant in the treatment with nano-formulated curcumin. The apoptosis and cell cycle analysis also confirmed that free and nano-formulated curcumin induces apoptosis and cell cycle arrest. Conclusion: Overall, the results suggested that curcumin loaded in niosomal nanoparticles effectively improves the anticancer effect and could be a capable approach for treating breast cancer.