Analyses of the combination of 6-MP and dasatinib in cell culture

Abstract

A major tenet of cancer therapeutics is that combinations of anticancer agents with different mechanisms of action and different toxicities may be effective treatment regimens. Evaluation of additivity/synergy in cell culture may be used to identify drug combination opportunities and to assess risk of additive/synergistic toxicity. The combination of 6-mercaptopurine and dasatinib was assessed for additivity/synergy using the combination index (CI) method and a response surface method in six human tumor cell lines including MCF-7 and MDA-MB-468 breast cancer, NCI-H23 and NCI-H460 non-small cell lung cancer, and A498 and 786-O renal cell cancer, based on two experimental end-points: ATP content and colony formation. Clonal colony formation by human bone marrow CFU-GM was used to assess risk of enhanced toxicity. The concentration ranges tested for each drug were selected to encompass the clinical Cmax concentrations. The combination regimens were found to be additive to sub-additive by both methods of data analysis, but synergy was not detected. The non-small cell lung cancer cell lines were the most responsive among the tumor lines tested and the renal cell carcinoma lines were the least responsive. The bone marrows CFU-GM were more sensitive to the combination regimens than were the tumor cell lines. Based upon these data, it appears that the possibility of enhanced efficacy from combining 6-mercaptopurine (6-MP) and dasatinib would be associated with increased risk of severe bone marrow toxicity, so the combination is unlikely to provide a therapeutic advantage for treating solid tumor patients where adequate bone marrow function must be preserved.

Enhanced Anticancer Effect of Green Synthesized Nanogold On Different Cell Lines

“…Band at 1628 cm -1 for AuNPs was discovered to be displaced to 1653 cm -1 for amide I band characteristic to C=O stretching of N-acetyl group, thus demonstrating that AuNPs are entirely confined with CS through affinity contact with amino group , band at 1423 cm -1 attributed to bending vibration of OH group was shifted to1413 cm -1 in AuNPs while at 1382 cm -1 assigned to the symmetric deformation vibration mode of CH3, 1322 cm -1 equivalent to the CH2 wagging vibration mode in primary alcohol, and 1258 cm -1 (corresponding to the vibration mode of the amide III due to the mixture of N-H deformation and C-N stretching) are not affected by occurrence of a metal surface. [39] Findings demonstrate that the hydroxyl and primary amino groups of CS were involved in the reduction and stabilisation of Au@CsNs. These characteristics matched those of Cs-AuNPs with cytotoxic activities in tumoral and leukemic cell lines that had been previously reported.…”