Background: Colorectal cancer is one of the world’s most lethal and dominant malignancies. The treatment efficiency of colorectal cancer is imperative due to its high metastasis rate. Chemotherapies drug used in the treatment of colorectal cancer causes drug resistance after a period of usage. Numerous studies have suggested the use of natural substances instead of chemotherapy drugs with side effects. Probiotics and bioactive compounds (e.g. curcumin) are substances of a natural origin that have been used to treat various types of cancers. Despite the advantages of bioactive substances, their use is restricted due to low bioavailability, insufficient solubility, and low dispersion rate in aqueous media. Nano-carriers such as niosome could pave the way for the efficient treatment of colon cancer. In this study, we used curcumin-loaded niosomal Nanoparticles (NPs) in combination with a heat-killed form of Saccharomyces cerevisiae as an anti-cancer agent against colorectal cancer cell line. Methods: Firstly, Saccharomyces cerevisiae yeast probiotic was cultivated and a heat-killed form of probiotic was obtained by heating in a water bath. Curcumin-loaded niosomal NPs (N-Cur) were synthesized with the thin film hydration method. The synthesized nanoparticles were characterized by DLS, FT-IR, SEM, and AFM techniques. These agents’ cytotoxicity and gene expression change effects were determined with MTT and real-time PCR, respectively. In order to investigate the effect of these agents on cell cycle arrest, apoptosis, and metastasis, additional flow cytometry and wound-healing tests were performed. Results: The result showed a higher decrease in the expression of genes involved in metastasis including COL10A1, MMP2, and MMP9 in the treatment of cancer cells with a combination of curcumin-loaded niosomal NPs and heat-killed form of Saccharomyces cerevisiae relative to the other forms. The superior result of apoptosis and cell cycle arrest among substances was achieved in
