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

Publication date: Available online 16 October 2019Source: Chemico-Biological InteractionsAuthor(s): Yasmeen M. Attia, Dina M. El-Kersh, Reham A. Ammar, Aliaa Adel, Aya Khalil, Hoda Walid, Kirullos Eskander, Mohamed Hamdy, Nada Reda, Nour Elhoda Mohsen, Ghada M. Al-Toukhy, Mohamed Tarek Mansour, Mohamed M. ElmazarAbstractTreatment 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 to PAX showed synergistic cytotoxic interaction on MCF-7 cells. The apoptotic potent...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research