Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the miR-149/let-7c/Faslg axis
FREE RADICAL RESEARCH
Authors: Zou, Liyuan; Ma, Xiaokun; Wu, Bingyuan; Chen, Yang; Xie, Dongmei; Peng, Chaoquan
Abstract
Ischaemia-reperfusion injury (IRI) is closely related to cardiovascular disease (CVD), which is the leading cause of death and disability. Exosomes appear to be involved in several diseases, including CVD. However, the role of mesenchymal stem cell (MSC)-derived exosomes in IRI remains unclear. miRNA expression levels in exosomes from rat normal MSCs or hypoxia-reoxygenation (H/R) MSCs were determined by qPCR and the two significantly upregulated miRNAs were selected for further investigation. Rat cardiomyoblasts (H9c2) were transfected with either miRNA mimics or scramble controls, followed by H/R induction. The effects of miRNA overexpression and exosome administration on H/R damage were then investigated. H/R increased Faslg, suppressed beta-catenin, inhibited cell proliferation and migration, and stimulated apoptosis and reactive oxygen species (ROS) production. miR-149 or Let-7c mimics or exosomes reversed H/R-induced damage. The luciferase reporter assay proved the targeted regulation of Faslg by both miR149 and Let-7c. Inhibition of beta-catenin suppressed cell migration, proliferation, and Delta psi m but increased apoptosis and ROS. Overall, bone marrow MSC-derived exosomes protected rat cardiomyoblasts from H/R injury via the miR-149/Let-7c/Faslg axis.
Olive leaf extract containing oleuropein modulates the cytotoxic effect of epirubicin on breast cancer cells depending on the cell line
TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI
Authors: Korkmaz, Seniz; Sarimahmut, Mehmet; Ozel, Mustafa Zafer; Ulukaya, Engin
Abstract
Objective: Epidemiologic studies showed that nutrition plays a role in incidence of cancer. However, little is known if nutrition also modulates the effect of chemotherapeutics. For this purpose, the present study investigates the cytotoxic effect of olive leaf extract and its combination with epirubicin. Method: Cell viability was measured via ATP assay on MDA-MB-231 and MCF-7 cell lines. Apoptosis was detected by poly(ADP-ribose) polymerase (PARP) cleavage, and the expression of apoptosis-related genes. A single extract was used throughout the study. Results: Both olive leaf extract and epirubicin resulted in cytotoxic effect in a dose-dependent manner in both cell lines. The extract further increased the cytotoxic effect of epirubicin in MDA-MB-231 cell line. However, in contrast, it abolished the cytotoxic effect of epirubicin in MCF-7 cell line. As a confirmative result, the increased expressions of FASLG and HRK following epirubicin treatment were down-regulated when epirubicin was used in combination with the extract in MCF-7 cells. Conclusion: Olive leaf extract modulates the cytotoxic effect of epirubicin when it is in combination depending on the type of cell line. This warrants further in vivo experiments for better understanding of this intriguing result.