Blue light emitting diodes irradiation causes cell death in colorectal cancer by inducing ROS production and DNA damage.

The light emitting diodes (LEDs) irradiation has been demonstrated to be potential therapeutic strategies for several diseases. However, the blue LED effects remain largely unknown in colorectal cancer (CRC), which is a major cause of morbidity and mortality throughout the world. In this study, we determined the effects of blue LED irradiation, the maximal light emission at 470 nm in wavelength, in human CRC cell lines SW620 and HT29. The cells were irradiated with blue LED light for 0 J/cm2, 72 J/cm2, 144 J/cm2, 216 J/cm2 and 288 J/cm2 respectively. We found that irradiation with blue LED light induced a marked decrease of live cells and an increase of dead cells. Additionally, lower cell proliferation and a remarkably increase of cell apoptosis were observed in blue LED-irradiated cells as compared with non-irradiated control group. The cell migration was significantly inhibited by blue LED irradiation 24, 48 and 72 h later compared with non-treated group. Blue LED-treated CRC cells further displayed a remarkably inhibition of EMT process in CRC cells. Finally, we found the accumulation of ROS production and DNA damage were induced by blue LED irradiation. These results indicated that blue LED irradiation inhibits CRC cell proliferation, migration and EMT process as well as induces cell apoptosis, which may result from increased ROS accumulation and induction of DNA damage.

By Targeting Atg7 MicroRNA-143 Mediates Oxidative Stress-Induced Autophagy of c-Kit+ Mouse Cardiac Progenitor Cells.

Therapeutic efficiency of cardiac progenitor cells (CPCs) transplantation is limited by its low survival and retention in infarcted myocardium. Autophagy plays a critical role in regulating cell death and apoptosis, but the role of microRNAs (miRNAs) in oxidative stress-induced autophagy of CPCs remains unclear. This study aimed to explore if miRNAs mediate autophagy of c-kit+ CPCs. We found that the silencing of miR-143 promoted the autophagy of c-kit+ CPCs in response to H2O2, and the protective effect of miR-143 inhibitor was abrogated by autophagy inhibitor 3-methyladenine (3-MA). Furthermore, autophagy-related gene 7 (Atg7) was identified as the target gene of miR-143 by dual luciferase reporter assays. In vivo, after transfection with miR-143 inhibitor, c-kit+ CPCs from green fluorescent protein transgenic mice were more observed in infarcted mouse hearts. Moreover, transplantation of c-kit+ CPCs with miR-143 inhibitor improved cardiac function after myocardial infarction. Take together, our study demonstrated that miR-143 mediates oxidative stress-induced autophagy to enhance the survival of c-kit+ CPCs by targeting Atg7, which will provide a complementary approach for improving CPC-based heart repair.

Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS.

BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS) is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. METHODS: BMSCs were exposed to ferric ammonium citrate (FAC) with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, ß-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS) level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. RESULTS: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 µg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. CONCLUSION: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.