Ali Mandegari, Azadeh Gholami-Javadie, Mandana Jafari, Salehe Sabouri,
Volume 28, Issue 170 (3-2019)
Abstract
Background and purpose: Combination therapy in cancer is a promising approach to increase efficacy and tolerability and to decrease adverse effects and drug resistance. Recently, anti-cancer properties of H2-receptor antagonists have been reported in several pre-clinical and clinical studies. The aim of this study was to examine the effect of cimetidine and famotidine H2-blockers on cytotoxicity of doxorubicin (DOX) on A549, MCF-7, and HT-29 human cancer cell lines.
Materials and methods: The cytotoxicity of cimetidine and famotidine, alone and in combination with DOX, was determined using MTT assay after 24 h incubation.
Results: Co-administration of H2-blockers with DOX led to an increase in cytotoxicity of the cell lines studied. While DOX at 1 μM could not reduce the viability of the cultured cells below 50%, its use in combination with cimetidine or famotidine at 25 μM reduced the percentage of viable cells below 50%.
Conclusion: Combination of cimetidine/famotidine with DOX could be a potential candidate for chemotherapy.
Iman Emrariani, Nourollah Sadeghzadeh, Saeid Abediankenari, Seyed Mohammad Abedi,
Volume 33, Issue 1 (11-2023)
Abstract
Background and purpose: The selection of co-ligand has a profound effect on the labeling efficiency, biodistribution, and tumor-targeting ability of 99mTc-labeled HYNIC-conjugated peptides. This study compared the in-vitro and in-vivo properties from the 99mTc-labeling of 6-Hydrazinonicotinamide-conjugated neurotensin (HYNIC-[βAla7-Tle12] NT (5-13)) by Tricine/EDDA and Tricine as two co-ligand systems.
Materials and methods: After radiolabeling, cellular specific binding, affinity and internalization were evaluated toward the HT-29 cell line, as neurotensin overexpressing cells for both of them. Finally, the biodistribution studies were performed on HT-29 xenografted tumor-bearing nude mice, and the imaging was performed using a gamma camera.
Results: The radiochemical purity of 99mTc labeled peptide with tricine and tricine/EDDA as co-ligands was found over 95%, and they showed desirable saline and serum stability up to 24 h. The dissociation constant (Kd) value for radiolabeled peptide with tricine and tricine/EDDA toward NT receptors were determined as 50.41 ± 9.76 and 32.66 ± 4.00, respectively. Internalization of radiolabeled peptide with tricine/EDDA was reported almost 2-fold more than radiolabeled peptide with tricine as co-ligand for HT-29 cell line after 4 h incubation. In biodistribution and imaging, the tumor/muscle activity ratio was 2.30 and 4.20, 1.74 and 2.28 at 2 h post-injection with tricine and tricine/EDDA, respectively.
Conclusion: Despite relatively similar radiochemical properties of both peptide radio-complexes with 99mTc, the complex labeled with a mixture of tricine/EDDA as co-ligands showed more suitable in vivo properties than tricine.
