Dexamethasone increases angiopoietin‐1 and quiescent hematopoietic stem cells: A novel mechanism of dexamethasone‐induced hematoprotection

Kim, Hyongbum; Choi, Ji Young; Lee, Jung Min; Park, Yoon Shin; Suh, Hwal; Song, Hae Ryong; Jo, Sangmee Ahn; Jo, Inho

doi:10.1016/j.febslet.2008.09.021

Cited by 12 publications

(9 citation statements)

References 30 publications

(38 reference statements)

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“…Such an explanation was recently proposed for the hematopoietic stem cell niche, where DEX provides bone marrow-and hemato-protection via fostering quiescence of the hematopoietic stem cell pool [39]. In the present work, although DEX inhibited the proliferation rate, the number of neurosphere forming units and thus, also the pool of active progenitors, was maintained.…”

Section: Multiple Effects Of Dex On Npcssupporting

confidence: 72%

Prolactin Induces MAPK Signaling in Neural Progenitors without Alleviating Glucocorticoid-Induced Inhibition of in vitro Neurogenesis

Wagner

Couillard‐Després²,

Lehner³

et al. 2009

Cell Physiol Biochem

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We recently demonstrated that prolactin (PRL) prevents chronic stress-induced inhibition of adult hippocampal neurogenesis. It remained unsettled, however, whether PRL is acting directly on neural stem and progenitors cells (NPCs) or if neurogenesis is affected by an indirect mechanism, for example through the extensively described effects of PRL on the HPA axis. To address this point, we used neurosphere cultures derived from the adult rat hippocampus as an in vitro model for NPCs. Dexamethasone (DEX) was applied to stress the NPCs, and proliferation, survival and differentiation of cells were examined. DEX markedly inhibited proliferation of NPCs and cells entered the G₀ phase of cell cycle. Moreover, DEX reduced NPC survival and repressed astroglial differentiation, which is normally induced by serum or bone morphogenetic protein application. Even though we could demonstrate that NPCs express the PRL receptor and ERK1/2 signaling is induced by PRL, we did not observe any effect of PRL on NPCs proliferation, differentiation or survival, neither in the presence nor during absence of DEX. In summary, our results indicate that PRL action on NPCs and neurogenesis in vivo occurs via an indirect mechanism.

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Section: Multiple Effects Of Dex On Npcssupporting

confidence: 72%

Prolactin Induces MAPK Signaling in Neural Progenitors without Alleviating Glucocorticoid-Induced Inhibition of in vitro Neurogenesis

Wagner

Couillard‐Després²,

Lehner³

et al. 2009

Cell Physiol Biochem

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“…However in those applications, dexamethasone is not included as a culture supplement, and thus the effects of co‐culture in combination with dexamethasone on HSPCs in vitro are not known. Studies investigating glucocorticoid treatment through intraperitoneal injections have shown hematoprotective effects of dexamethasone, promoting the quiescence of stem cells as seen in the maintenance of high colony‐forming cell numbers even after cytotoxic chemotherapy 29, 30. In exploring how HSPCs affect the progression of MSCs initiated toward osteogenic differentiation via dexamethasone exposure, we observed that dexamethasone may play a role in maintaining hematopoietic stem and progenitor cells in vitro.…”

Section: Discussionmentioning

confidence: 90%

Investigating the role of hematopoietic stem and progenitor cells in regulating the osteogenic differentiation of mesenchymal stem cells in vitro

Liao

Hammerick

Challen

et al. 2011

Journal Orthopaedic Research

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Significant progress has been made in understanding the hematopoietic supportive capacity of both mesenchymal stem cells (MSCs) and osteogenic cells in maintaining hematopoietic stem and progenitor cells (HSPCs) in vitro. However the role of HSPCs in regulating their bone marrow niche environment through influencing the function of neighboring cell populations to complete this reciprocal relationship is not well understood. In this study, we investigated the influence of HSPCs on the osteogenic differentiation of MSCs in vitro, using a highly enriched population of hematopoietic cells with the phenotype c-Kit+Sca-1+Lineage− (KSL) and bone marrow derived mesenchymal stromal cells in direct contact co-culture in medium with or without the addition of the osteogenic supplement dexamethasone. The data suggest that a low dose of HSPCs in co-culture with MSCs in combination with dexamethasone treatment accelerates the osteogenic progression of MSCs, as evidenced in the earlier peak in alkaline phosphatase activity and enhanced calcium deposition compared to cultures of MSCs alone. We observed a longer persistence of functional primitive hematopoietic stem and progenitor cells in the population treated with dexamethasone, and this observation was positively correlated with enhanced osteogenic differentiation of MSCs. Therefore, our findings further support the concept that HSPCs are actively involved in regulating the development and maintenance of the stem cell niche environment in which they reside.

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“…The assay was based on the measurement of activity of LDH released from the damaged cells into the medium (Kim et al, 2008). Cells were plated in the 96-well plates (1 Â 10 4 cells per well) and incubated for 24 h. Euphorbia hirta extract was introduced separately to the cells with different concentrations (50, 25, 12.5, 6.25, 3.125, and 1.5625 mg/mL) and incubated for another 24 h. The positive control was prepared by adding 1% Triton of lysis solution to the control cells at 45 min prior to the centrifugation.…”

Section: Lactate Dehydrogenase Leakage Assaymentioning

confidence: 99%

Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction byEuphorbia hirtain MCF-7 breast cancer cells

Kwan

Saito

Demirtaş

et al. 2015

Pharmaceutical Biology

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Context: Euphorbia hirta L. (Euphorbiaceae) has been used as a folk remedy in Southeast Asia for the treatment of various ailments. Objective: The current study evaluates the cytotoxicity, cell-cycle arrest, and apoptotic induction by E. hirta in MCF-7 breast cancer cells. Materials and methods: Cytotoxic activity of methanol extract of whole part of E. hirta was determined by the MTT assay at various concentrations ranging from 1.96 to 250.00 mg/mL in MCF-7 cells. Cell morphology was assessed by light and fluorescence microscopy. Apoptosis and cell-cycle distribution were determined by annexin V staining and flow cytometry. DNA fragmentation, caspase activity, and reactive oxygen species (ROS) assays were performed using the commercially available kits. To identify the cytotoxic fraction, E. hirta extract was subjected to bioassay-guided fractionation. Results: Euphorbia hirta exhibited significant inhibition of the survival of MCF-7 cells and the half inhibitory concentration (IC 50 ) values was 25.26 mg/mL at 24 h. Microscopic studies showed that E. hirta-treated cells exhibited marked morphological features characteristic of apoptosis. Euphorbia hirta extract also had an ignorable influence on the LDH leakage and generating intracellular ROS. The flow cytometry study confirmed that E. hirta extract induced apoptosis in MCF-7 cells. Euphorbia hirta also resulted in DNA fragmentation in MCF-7 cells. Moreover, E. hirta treatment resulted in the accumulation of cells at the S and G 2 /M phases as well as apoptosis. The caspase activity study revealed that E. hirta extract induced apoptosis through the caspase-3-independent pathway by the activation of caspase-2, 6, 8, and 9. Euphorbia hirta hexane fraction, namely HFsub4 fraction, demonstrated highest activity among all the fractions tested with an IC 50 value of 10.01 mg/mL at 24 h. Discussion and conclusion: This study revealed that E. hirta induced apoptotic cell death and suggests that E. hirta could be used as an apoptosis-inducing anticancer agent for breast cancer treatment with further detailed studies.

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Dexamethasone increases angiopoietin‐1 and quiescent hematopoietic stem cells: A novel mechanism of dexamethasone‐induced hematoprotection

Cited by 12 publications

References 30 publications

Prolactin Induces MAPK Signaling in Neural Progenitors without Alleviating Glucocorticoid-Induced Inhibition of in vitro Neurogenesis

Prolactin Induces MAPK Signaling in Neural Progenitors without Alleviating Glucocorticoid-Induced Inhibition of in vitro Neurogenesis

Investigating the role of hematopoietic stem and progenitor cells in regulating the osteogenic differentiation of mesenchymal stem cells in vitro

Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction byEuphorbia hirtain MCF-7 breast cancer cells

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