Infections caused by resistant strains of Acinetobacter baumannii are now a global problem that requires the immediate development of new antimicrobial drugs. Combination therapy is one of the strategies used to solve this problem. Based on this information, the purpose of this study was to determine whether quercetin (QUE), in combination with three antibiotics, is effective against colistin-resistant A. baumannii strains (ColR-Ab). The effects of the combination of QUE with colistin (COL), amikacin (AMK), and meropenem (MEM) were evaluated according to the checkerboard synergy test. The combinations of QUE + COL and QUE + AMK showed synergistic activity on ColR-Ab strains with FICI values in the range of 0.1875–0.5 and 0.1875–0.2825, respectively. A 4- to 16-fold decrease in COL MIC and a 16- to 64-fold decrease in AMK MIC values were detected. Synergistic activity was confirmed by the time-kill test, and these combinations were found to be bactericidal at the end of 24 h. According to spectrophotometric measurements, the combinations of QUE + COL and QUE + AMK induced membrane damage, leading to the leakage of nucleic acids. Cell lysis and cell death were confirmed with SEM observations. The detected synergy offers an opportunity for the future development of treatment strategies for potential infections caused by ColR-Ab strains.
Surgery, chemotherapy and radiotherapy, which are known as conventional cancer treatments, have been applied for more than 40 years. Because the target of chemotherapy is tumor cells, treatment agents are used at high doses during application and this creates toxic responses, causing side effects in normal cells. Furthermore, due to the high doses, cancer cells develop resistance to the agent and, as a result, success of the treatment gradually decreases. That is why chemotherapy is combined with various other cancer treatments to increase the therapeutic efficacy while reducing the side effects. In this study, the cytotoxic effect of endostatin, vinorelbine and their combination on breast cancer cell line MDAMB 231 was researched in vitro. In addition, the effects caused by the combination on TRAIL, TNF-α and caspase-2, 3, 6, 8 and -9 proteins, which undertake key roles in apoptosis were investigated. Cytotoxic effects of both agents and their combinations on normal epithelial cells (293 T) were also studied and compared. We found that endostatin is cytotoxic for cancer cells through caspase-8 and TNF-α activation, which affects the extrinsic pathway of apoptosis Combining endostatin as an anti-angiogenic agent with vinorelbine ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 19 (1): gmr18497 A. Cansu Kilit et al. 2 significantly suppressed the cytotoxicity that vinorelbine exerts on normal cells.
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