Inhibition of aldehyde dehydrogenase-1 and p-glycoprotein-mediated multidrug resistance by curcumin and vitamin D3 increases sensitivity to paclitaxel in breast cancer.

Inhibition of aldehyde dehydrogenase-1 and p-glycoprotein-mediated multidrug resistance by curcumin and vitamin D3 increases sensitivity to paclitaxel in breast cancer. Chem Biol Interact. 2019 Oct 16;:108865 Authors: Attia YM, El-Kersh DM, Ammar RA, Adel A, Khalil A, Walid H, Eskander K, Hamdy M, Reda N, Mohsen NE, Al-Toukhy GM, Mansour MT, Elmazar MM Abstract Treatment of breast cancer by paclitaxel (PAX) often encounters therapeutic failure most likely caused by innate/acquired resistance. Cancer stem cells (CSCs) and multidrug resistance complex (MDR-1 or P-glycoprotein) overexpression are main mechanisms implicated in chemoresistance. Increased aldehyde dehrogenase-1 (ALDH-1) was previously correlated with the stemness features of CSCs and hence is used as a marker for identification and CSCs targeting. The present study, therefore, aimed at investigating the effect of both curcumin (CUR) and vitamin D3 (D3) on MDR-1 and ALDH-1 expression and consequently the resistance to PAX both in vitro and in vivo. CUR was isolated and identified using UPLC-ESI-MS/MS. For in vitro studies, the antiproliferative effect of PAX, CUR, 1,25(OH)2D3 (the active form of D3, also known as calcitriol) was determined, each alone and combined (PAX + CUR, PAX+1,25(OH)2D3, and PAX + CUR+1,25(OH)2D3) using MCF-7 breast cancer cells. Ehrlich ascites carcinoma solid tumor animal model was also used for in vivo studies. Combining CUR and/or 1,25(OH)2D3 t...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research