Search

Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated the anticancer mechanism of these compounds. Cytotoxicity assays were performed against untransformed cells and against breast cancer cell MCF-7. Apoptosis analysis and in-vitro migration assay were also performed to evaluate the mechanism of induction of cell death. All thiophene derivatives reduced the cell viability in breast cancer cells, showing cytotoxic activity (IC5030 µmol/l), and SB-200 compound showed the best selectivity index in MCF-7 cells compared with doxorubicin in 2D culture. All thiophene derivatives significantly induced G0/G1 phase cell cycle arrest. However, only SB-83 treatment was effective against motility of MCF-7 cells in 2D culture (P=0.0059). The SB-200 derivative treatment induced an increased proportion of acridine orange/Hoechst double-stained cells (35.35 vs. 3.14%, P=0.0002) compared with nontreated cells, with apoptosis morphological alterations independent of caspase 7 activation (P0.05). MCF-7 cells became less responsive to SB-200 and to doxorubicin in 3D culture compared with cells in 2D culture (higher IC50 values); however, SB-200 showed a better cytotoxic effect compared with doxorubicin in 3D culture. Therefore, the current study provides an insight into anticancer potential of thiophene derivatives, and further studies should be conducted to understand the mechanism by which thiophene derivatives act on cancer cells.

Introduction: The role of the immune and inflammatory pathways in diabetic patients with coronary artery disease (CAD) is important but not complete understood. The aim of this study was to evaluate concentrations of the interleukins 17 A and 22 in diabetic patients with stable CAD. Hypothesis: Interleukins 17 A and 22 are not increased in diabetic patients with stable CAD. Methods: This is a cross-sectional, prospective, analytical study, conducted from August to December 2012. We included 15 diabetic patients (P) with stable CAD, CCS III or IV, ischemic myocardial scintigraphy, who had not been subjected to any kind of myocardial revascularization and with coronary stenosis ≥ 50% according to current coronary angiography. There were 20 healthy volunteers (C), to take up comparison of concentrations of interleukins (IL). Interleukins were evaluated in serum of patients and after 48 hours of cells in culture with and without stimulus. IL concentrations were expressed in pg / ml. Statistical analysis was performed using the Mann-Whitney or Student t test. P ≤ 0,05 was considered statistically significant. Results: There were 6 men and 9 women in the group of the diabetic patients and 12 men and 8 women in the controls. The age was similar between the groups (61.6 ± 6.7 years vs 57.9 ± 9.4, p = ns). The main CAD risk factors: hypertension 73%, smoking 60%, dyslipidemia 40%, prior myocardial infarction 33%. The comparison between the groups showed: IL 17 A: Serum: P = 3.91 (3.91 -- 3.91 ) vs C = 3.91 (3.91 -- 3.91 ), p = 0.82; culture 48 hours without stimulus: P = 3.91 (3.91 -- 3.91) vs C = 3.91 (3.91 -- 3.91), p = 0.06; culture 48 hours with stimulus: P = 199 (3.91 -- 520) vs C = 154 (3.91 -- 574), p = 0.90. IL 22: Serum: P = 15.63 (15.63 -- 41.09) vs C = 15.63 (15.63 -- 41.09), p = 0.34; culture 48 hours without stimulus: P = 7.81 (7.81 -- 7.81) vs C = 7.81 (7.81 -- 7.81), p = 0.09; culture 48 hours with stimulus: P = 113.79 (7.81 - 248.63) vs C = 322.87 (7.81 - 628.49), p = 0.14. Conclusions: There were no differences in concentrations of IL 17 A and 22, does not matter in serum or cell in culture. In conclusion in diabetic patients with stable CAD the concentrations of interleukins 17 A and 22 were not increased.