Trehalose reduces the number of Stress Granules in cancer-resistant cells, increasing Sorafenib and Gemcitabine sensitivity

Backgrounds: Trehalose is a disaccharide composed of Monomeric glucose units combined byglycosidic linkage and linked at anomeric carbon by α bonding. It serves as a structural andtransport disaccharide for cellular components and a stress-protective mechanism formembranes. Trehalose, which has antioxidant properties, has an anti-cancer effect, which isexplained by targeting cell progression, angiogenesis, and metastasis pathways at the molecularlevel within the cell. Sorafenib and Gemcitabine are among the anti-cancer drugs used for arange of malignancies. One mechanism of resistance to these chemotherapy drugs is thepreferential retention of ATF۴ expression by encoding its mRNA in the structure ofribonucleoproteins formed in cancer cells under stresses that cause translation stoppage, knownas stress granules (SGs). Trehalose may be a viable option for reducing the number of SGs byincreasing the dephosphorylation of eIF۲α, a key component of the SGs formation pathway.Materials and Methods: The number of SGs in Sorafenib and Gemcitabine-resistant cancercells was determined using the protein markers TIA-۱ and PABP۱. The sensitivity to theSorafenib and Gemcitabine and ATF۴ expression level was measured before and after usingTrehalose.Results: Trehalose reduced the number of SGs, decreased ATF۴ expression, and increasedsensitivity to Sorafenib and Gemcitabine in resistant cancer cells.Conclusion: Trehalose reduces the number of SGs by increasing eIF۲α dephosphorylation andcan be used in combination with Sorafenib and Gemcitabine in cancer cells resistant to both toincrease efficiency and increase sensitivity.