In the present study, we investigated the antiproliferative activity of Naja ashei full venom (NAV) on human colorectal cancer cells. The NAV-induced antiproliferative effect was associated with cell cycle arrest in S phase and increased number of cells with sub G0/G1 DNA content, which is considered a marker of apoptosis. Apoptosis has also been confirmed with annexin V/PI staining. Furthermore, flow cytometric analysis revealed loss of mitochondrial membrane potential with concomitant increase in cytochrome c and Smac/DIABLO protein content. These effects were associated with the activation of caspase-9 and caspase-3, as well as with PARP cleavage. Moreover, phosphorylation of antiapoptotic Bcl-2 protein in NAV-treated HCT116 was observed. In conclusion, our study for the first time documented antiproliferative/pro-apoptotic effect of NAV in colorectal cancer cells. Our results strongly suggest the involvement of mitochondria in NAV induced apoptosis of cancer cells. Future studies are needed to further examine the potential of NAV in the treatment of colon cancer.
Objectives: To assess the clinical effect of ivabradine on coronary artery disease and heart failure compared with placebo or standard care via clinical trials or meta-analysis. Design: Systematic review and meta-analysis - searches of electronic databases from 2003 to 2018. Data Extraction: Study results relating to benefit, risk and uses of ivabradine were extracted with individually meta-analysis or clinical trials. Results: The primary analysis included 1413 records (keyword – ivabradine), of which 53 clinical studies were separated using the PRISMA-flow diagram with the following conclusion. The drug ivabradine has a positive effect on heart rate reduction in heart failure and other cardiovascular diseases. The health status of patients treated by ivabradine is generally better compared to patients with a placebo. Across the analysed trials, placebo, β-blockers, amlodipine or ranolazine were commonly used as control drugs in the control group. Ivabradine has been generally used as a replacement β-blockers in patients suffering from side effects. However, the effect of ivabradine is manifested only in patients with high heart rate (≥70/min.) and left ventricular dysfunction. We showed that ivabradine treatment is associated with an increased risk of the atrial fibrillation (AF), and the side effect is substantially more common than 1:10 000, presently reported in the product specification. This extent of AF incidence has not been previously reported in clinical trials. Conclusion: Ivabradine treatment improved cardiopulmonary function and increased the exercise capacity patients with chronic heart failure. Ivabradine reduced mortality and hospitalization risk and improved the quality of life. Ivabradine appears to show better efficacy in comparison with β-blockers treatment, but this finding requires further study and clinical trials.
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