Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

Abstract

Myelodysplastic syndrome (MDS) is regarded as a spectrum of bone marrow failure disorders that share hemato‐pathological state of cellular dysplasia and cytopenia. The modern treatment of cancers like chemotherapy and radiation therapy sometimes severely pounce on the basic hematopoietic stem/progenitor cellular (HSPC) compartment which gradually disclose the clinical symptoms of MDS. The present study involves flowcytometric protein expression analysis of insulin growth factor receptor (IGFR), PI3K‐Akt‐mTOR pathway, the autophagy related proteins (ATG's), the status of antioxidative molecules SOD2 and SDF1 and apoptosis profiling in ethyl‐nitroso‐urea induced myelodysplasia. The redox status that is, reactive oxygen species was estimated with dihydroetidium and the status of mitochondria and lysosomes were checked by Janus green B and neutral red staining respectively, pre and post quercetin treatment in MDS bone marrow. The results revealed the activated IGFR/PI3K/Akt axis in MDS bone marrow but unconventionally both p‐mTOR and autophagy (p‐ATG1, p‐AT6, ATG7, ATG12) was downregulated. Interestingly, post quercetin treatment an upregulation of basal autophagocytosis, reversal of oxidative damage and proper functionality of mitochondria and lysosome was recorded. Taken together, the study hinted that the PI3K‐Akt‐mTOR pathway does not rule over the process of autophagocytosis in HSPC's of MDS bone marrow and the isoflavanoid quercetin remarkably restored autophagocytosis and hematopoietic oxidative status toward normalcy during the progression of myelodysplasia.

Quercetin in Tartary Buckwheat Induces Autophagy against Protein Aggregations

“…However, in contrast with our findings, their study reported that quercetin treatment induced protein aggregation, mostly inside the nucleus [ 29 ]. Induction of autophagy by quercetin has been observed in several tissues and diseases, including diabetic nephropathy [ 30 ], oocytes from aged mice [ 31 ], intervertebral disc degeneration [ 32 ], myelodysplastic bone marrow [ 33 ], and human retinal pigment epithelial cells [ 34 ], while one study reported that quercetin attenuated autophagy in a rat model of traumatic brain injury [ 35 ]. Regardless of these previous studies, here we performed a comprehensive set of autophagy assays that unquestionably proved the effect of quercetin on autophagy for the first time [ 36 ].…”

Mitophagy suppression by miquelianin‐rich lotus leaf extract induces ‘beiging’ of white fat via AMPK/DRP1‐PINK1/PARKIN signaling axis

“…Use of Janus Green B is an indirect method to assess mitochondrial dysfunction as the contents escape in the cytosol upon the rupture of the mitochondrial membrane, leading to colorant oxidation 10 . Briefly, the cells were stained with Janus Green B for 5 min, after which they were observed under an optical microscope (Axio Vert.A1, Germany).…”

Environmental pollutant N‐N′ethylnitrosourea‐induced leukemic NLRP3 inflammasome activation and its amelioration by Eclipta prostrata and its active compound wedelolactone

“…Disease development and post treatment effects were confirmed by performing peripheral blood hemogram 36,39,46–48 . Total RBC and WBC counts were determined by standard laboratory protocol, using hemocytometer chamber (Rohem, India).…”