Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs)

Abstract

BackgroundThis study investigated the effect of Astragalus polysaccharides (APS) on radiation-induced bystander effects (RIBE) in human bone mesenchymal stem cells (BMSCs) induced by irradiated A549 cells.Material/MethodsA549 cells were irradiated with 2 Gy X-rays to obtain conditioned medium. BMSCs were incubated with the conditioned medium or APS. The levels of reactive oxygen species (ROS) and TGF-β were detected by ELISA. Cell survival, genomic instability, and DNA damages were detected by CCK-8 assay, colony formation assay, the micronucleus test and immunofluorescence assay, respectively. The protein and phosphorylation protein expression of p38, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK1/2), P65, and cyclooxygenase-2 (COX-2) in bystander effect cells were detected by Western blot.ResultsThe expression of COX-2 and ROS increased following stimulation with conditioned medium; this effect was inhibited by pre-exposing the cells to APS. BMSCs growth and colony formation rate decreased following stimulation with conditioned medium; this effect was suppressed by pre-exposing the cells to APS. In addition, the micronucleus rate and 53BP1 foci number increased after treatment with conditioned medium; this increase in BMSCs was inhibited by APS. The levels of phosphorylated p38, JNK, ERK1/2, NF-κB P65, and COX-2 proteins were increased by conditioned medium but were decreased by pre-treatment with APS.ConclusionsRIBE in BMSCs induced by the irradiated A549 was mediated by the ROS in the conditioned medium and might be related to MAPK/NF-κB signal pathways in BMSCs. APS may block RIBE through regulating the MAPK/NF-κB pathway.

Astragalus polysaccharide protects formaldehyde-induced toxicity by promoting NER pathway in bone marrow mesenchymal stem cells

“…This indicates that APS may protect against genotoxicity in BMSCs exposed to FA. This is consistent with study showing that APS can maintain genomic stability and reduces DNA damage in BMSCs incubated with the irradiated A549 [22,29]. When external factors induce DNA damage, the cells can mobilize corresponding repair mechanisms to reverse these damages in order to maintain genetic stability.…”

The Effects of Astragalus Polysaccharide on Bone Marrow-Derived Mesenchymal Stem Cell Proliferation and Morphology Induced by A549 Lung Cancer Cells

“…APS has been shown to inhibit cell apoptosis, and reduce the proliferation and differentiation of bone marrow-derived MSCs following ferric ammonium citrate-induced iron overload [21]. Zhang et al reported that APS had protective effects on cell survival level of bystander cells cultured in conditioned medium and maintained the stability of the genome by reducing the number of 53BP1 foci and micronuclei [22]. Current understanding of the effects of APS on bone marrow-derived MSCs in the lung cancer microenvironment remains unknown.…”

“…Recent studies have shown that APS can reduce the proliferation of bone marrow-derived MSCs caused by ferric ammonium citrate-induced iron overload [21]. Treatment with APS also inhibits ionizing radiation-induced bystander effects in bone marrow-derived MSCs [22], has significant antitumor activity in human lung cancer cells [23], and exerts a protective effect on injury due to inflammation [24]. However, the role of APS in bone marrow-derived MSCs induced by lung cancer cells remains to be investigated.…”

Promoting Reactive Oxygen Species Generation: A Key Strategy in Nanosensitizer-Mediated Radiotherapy

“…Similarly, Zhang et al used conditioned medium obtained after radiation to culture bone marrow-derived mesenchymal stem cells and observed the effect of RIBEs. They found that the RIBEs in these cells were mediated by ROS, which may be related to the MAPK/NF-κB signaling pathway [113].…”