ABSTRACT
Disulfiram and hydralazine have recently been reported to have anti-cancer action, and repositioned to be used as adjuvant in cancer therapy. Chemotherapy combined with other medications, such as those that affect the immune system or epigenetic cell profile, can overcome resistance with fewer adverse effects compared to chemotherapy alone. In the present study, a combination of doxorubicin (DOX) with hydrazine (Hyd) and disulfiram (Dis), as a triple treatment, was evaluated against wild-type and DOX-resistant MCF-7 breast cancer cell line. Both wild-type MCF-7 cell line (MCF-7_WT) and DOX-resistant MCF-7 cell line (MCF-7_DoxR) were treated with different combination ratios of DOX, Dis, and Hyd followed by measuring the cell viability using the MTT assay. Synergism was determined using a combination index, isobologram analysis, and dose-reducing index. The anti-proliferation activity and mechanism of the triple combination were investigated by apoptosis analysis. The results showed a reduction in the IC50 values of DOX in MCF-7_WT cells (from 0.24 µM to 0.012 µM) and MCF-7_DoxR cells (from 1.13 µM to 0.44 µM) when treated with Dis (0.03µM), and Hyd (20µM) combination. Moreover, The triple combination DOX/Hyd/Dis induced significant apoptosis in both MCF-7_WT and MCF-7_DoxR cells compared to DOX alone. The triple combination of DOX, Dis, and Hyd showed a synergistic drugs combination to decrease the DOX dose needed to kill both MCF-7_WT and MCF-7_DoxR cancer cells and enhanced chemosensitivity to DOX.
ABSTRACT
Helicobacter pylori (H. pylori) infection is a global issue. Its eradication in affected individuals is important to prevent several further complications that may occur if left untreated. Proton pump inhibitors (PPIs) serve an important role in the eradication regimens of H. pylori. PPIs are metabolized primarily through the CYP2C19 enzyme in the liver. Inter-individual variation in the response to eradication treatment may partly be due to variations in the metabolism of PPIs. The aim of this study was to determine whether there was any association between CYP2C19 genetic polymorphisms and the response to eradication therapy amongst Jordanians infected with H. pylori receiving lansoprazole-based regimens. The present study was approved by the Institutional Review Board of The University of Jordan Hospital. A total of 141 patients infected with H. pylori were genotyped for the polymorphisms CYP2C19*2 and CYP2C19*17 using the PCR-restriction fragment length polymorphism assay method. Patients received lansoprazole-based triple or sequential therapy. The assessment of eradication was performed using either a H. pylori stool antigen test or from feedback from patients regarding their improvement. Eradication rates were 84.6% and 64.5% in the intermediate-metabolizer and extensive-metabolizer group, respectively. This difference was not statistically significant. Moreover, no significant association was found between the carriers of the CYP2C19*17 polymorphism and the response to eradication therapy. These findings suggest that there was no significant association between the CYP2C19 genotype and the response to eradication therapy amongst Jordanians infected with H. pylori.