Anti-apoptotic effect of insulin on normal hepatocytes in vitro and in vivo

APOPTOSIS ◽  
2004 ◽  
Vol 9 (5) ◽  
pp. 609-617 ◽  
Author(s):  
M. Bilodeau ◽  
J. Tousignant ◽  
C. Éthier ◽  
B. Rocheleau ◽  
V.-A. Raymond ◽  
...  
Keyword(s):  
Apoptotic Effect

scholarly journals Epibrassinolide Promotes the Apoptotic Potential of Gemcitabine in Pancreatic Cancer Cells

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 10
Author(s):  
Kuryayeva ◽  
Arisan ◽  
Gurkan ◽  
Yerlikaya
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Options ◽  
Flow Analysis ◽  
Nuclear Condensation ◽  
Pancreatic Cancer Cells ◽  
Incidence And Mortality ◽  
Apoptotic Effect ◽  
Mitochondrial Membrane Potential Loss

Pancreatic cancer is a lethal disease for which the incidence and mortality rates are close. Patients with advanced stage have median survival of three months. Gemcitabine (GEM), the anticancer analog of deoxycytidine, has been considered standard care of pancreatic cancer. However, disease progression usually occurs. Despite the effort for better treatment options, phase trials fail due to severe side effects. Epibrassinolid (EBR) is a member of brassinnosteroids with similar chemical structure to steroid hormones. Our group showed that EBR induces apoptosis via endoplasmic reticulum stress induction both in in vitro and in vivo cancer models, without effecting non-cancerous cells or non-tumor bearing mouse. Our aim in this study is to evaluate whether EBR has the potential to increase the apoptotic effect of GEM in AsPc1 pancreatic cells. We showed by MTT assay that EBR has apoptotic efficiency in AsPc1 cells and it also increases the cell viability loss when combined with GEM. The combination of EBR (30 µM) and GEM (100 µM) further increases mitochondrial membrane potential loss and nuclear condensation. In addition, exposure of cells to EBR and GEM co-treatment induces subG1 apoptotic population showed by FACS flow analysis. Consequently, we suggest that the effect of GEM can be increased with EBR combination.

scholarly journals Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5250
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
Seung-Hwan Yang
Keyword(s):  
Biological Activities ◽  
Neuroprotective Effect ◽  
In Vivo Studies ◽  
Amnesic Effect ◽  
In Vivo Experiments ◽  
Toxicological Studies ◽  
Apoptotic Effect ◽  
Pharmaceutical Industries

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Mediation of HER2 expression-dependent antiproliferative and pro-apoptotic effect of pan-HER2-specific TKIs on breast cancer cells through STAT5 and JNK.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11606-e11606
Author(s):  
Daphne Gschwantler-Kaulich
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Her2 Expression ◽  
Her Family ◽  
Proliferation And Apoptosis ◽  
Apoptotic Effect

e11606 Background: HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. Methods: Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP and immunolabeling for active caspase 3, respectively. Results: All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines, irrespective of their sensitivity against the HER-TKIs. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. Conclusions: We have shown that HER-TKIs exert a HER2 expression-dependent effect on proliferation and apoptosis in cancer cell lines in vitro, which is at least partially mediated by blockade of JNK and STAT5A/B. Despite slight differences in their specificity towards individual members of the HER family all three inhibitors had comparable antiproliferative and proapoptotic effects in vitro.

scholarly journals Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 291-299 ◽  
Author(s):  
Mehmet Uzumcu ◽  
Zui Pan ◽  
Yi Chu ◽  
Peter E Kuhn ◽  
Rob Zachow
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Interstitial Cells ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Apoptotic Effect ◽  
Equine Chorionic Gonadotropin ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) regulates granulosa cell (GC) steroidogenesis and suppresses apoptosis in non-ovarian cells. The hypothesis was thus developed that intraovarian HGF supports folliculogenesis by mediating steroidogenesis and suppressing apoptosis. To investigate the latter, the anti-apoptotic actions of HGF were tested in GCs and follicles isolated from immature rats. Results showed that HGF suppressed apoptosis in GC and follicle cultures as visualized using apoptosis indicator dye, YO-PRO-1. Immunohistochemistry was used to investigate the distribution of HGF, c-met, and HGF activator (HGFA) protein during folliculogenesis in equine chorionic gonadotropin (eCG)-primed rats. Immunoreactive HGF content was the greatest in GCs within preantral follicles. Following eCG, large antral follicles showed elevated HGF staining in theca and interstitial cells when compared with GCs. Intense c-met staining was observed in GCs within non-primed small preantral follicles; following eCG, the level of c-met was diminished in GCs, but increased within theca and interstitial cells. Theca, interstitium, and GCs in non-primed and primed ovaries contained HGFA. Following eCG, HGFA was more apparent in theca cells and the interstitium when compared to that in GCs within large antral follicles. The presence of HGF, c-met, and HGFA in preantral follicles would potentially enable the anti-apoptotic effects of HGF that were observed in vitro to occur in vivo. Advanced folliculogenesis led to a change in the cellular distribution of the HGF, c-met, and HGFA, suggesting that the ovarian HGF system is hormonally regulated in vivo.

scholarly journals Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces

2021 ◽  
Vol 14 (7) ◽  
pp. 623
Author(s):  
Masoud Moghadaszadeh ◽  
Mehdi Khayyati ◽  
Adel Spotin ◽  
Roghayeh Norouzi ◽  
Abdol Sattar Pagheh ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Cystic Hydatid Disease ◽  
Liposomal System ◽  
Physico Chemical ◽  
Apoptotic Effect ◽  
Apoptotic Activity

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 μg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 μg/mL and 400 μg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

Abstract 629 Secreted Frizzled Related Protein 2 Protects Cells from Apoptosis by Blocking the Effect of Canonical Wnt3a

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zhongyan Zhang ◽  
Arjun Deb ◽  
Alok Pachori ◽  
Wei He ◽  
Jian Guo ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Solid Phase ◽  
Tunel Staining ◽  
Beta Catenin ◽  
Related Protein ◽  
Wnt Ligands ◽  
Apoptotic Effect ◽  
Induced Apoptosis

We have demonstrated that mesenchymal stem cells (MSCs) overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and in vitro through the release of secreted frizzled related protein 2 (Sfrp2). However, the mechanisms mediating these effects of Sfrp2 have not been fully elucidated. In this study, we test the hypothesis that Sfrp2 exerts anti-apoptotic effect by antagonizing pro-apoptotic properties of specific Wnt ligands. To explore this possibility, we studied rat cardiomyoblasts subjected to hypoxia reoxygenation (HR) injury. We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. We choose to study Wnt3a because its expression is up-regulated in response to hypoxia. Wnt3a (3nM) significantly increased cellular caspase activities (35% increase, p<0.05, n=3) and TUNEL staining (38% increase) in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion (0nM, 8.50±0.47; 3nM, 7.28±1.03; 30nM, 7.45±0.49; 300nM, 5.65±0.35), achieving 36% inhibition at a concentration of 300nM. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that 600nM Sfrp2 inhibits 47% of the beta-catenin / TCF transcriptional activities induced by Wnt3a(0.55±0.07 vs 1.03±0.04). Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities by 31% and 77% respectively (caspase activities: 8.62±0.05 vs12.54±0.49; transcriptional activities: 0.41±0.03 vs 1.77±0.01) Similarly, siRNA against beta-catenin inhibited the Wnt3a-activated caspase activities by 59% (6.44±0.92 vs 15.71±0.67). Consistent with this, significantly fewer TUNEL positive cells were observed in siRNA transfected cells than in control cells (43% decrease). Together, our data provide strong evidence to support the notion that Wnt3a is a canonical Wnt with pro-apoptotic action whose cellular activity is prevented by, at least in part, Sfrp2 through direct binding of these molecules. These results can explain the in vivo protective effect of Sfrp2 and highlight its therapeutic potential for the ischemic heart.

Recombinant PDGF-BB Enhances Platelet Recovery in Mice with Radiation Induced Thromobocytopenia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1232-1232
Author(s):  
Jie Yu Ye ◽  
Godfrey ChiFung Chan ◽  
Shing Chan ◽  
Jue Cong Luo ◽  
Mo Yang
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Imatinib Mesylate ◽  
Pdgf Receptor ◽  
Hematopoietic Stem ◽  
Platelet Production ◽  
Apoptotic Effect ◽  
Radiation Induced

Abstract Platelet-derived growth factor (PDGF) involves in the regulation of hematopoietic stem cells. Imatinib mesylate (Gleevec), a PDGF receptor inhibitor, induces thrombocytopenia in 50% of patients with chronic myeloid leukaemia (CML). Our previous studies showed that PDGF enhances megakaryocytopoiesis in vitro via its receptors directly. However, the in vivo effect of recombinant PDGF in thrombocytopenic models has not been reported. In this study, we investigated the in vivo effect of PDGF as well as thrombopoietin (TPO) on hematopoietic stem cells and platelet production in a radiation treated mouse model. We also explored its potential molecular mechanisms on thrombopoiesis. A radiation induced myelosuppression with thrombocytopenic model was established using 4-Gy-irradiated mice. PDGF-BB (1 mg/kg/day) and TPO (1 mg/kg/day) were injected separately after radiotherapy into the mice. Peripheral blood platelets, WBC and RBC from PDGF-BB, TPO and control groups were collected and analyzed on day 0, 7, 14 and 21 respectively. The mice were sacrificed on day 21 and their bone marrows were harvested for CFU assays and histology analysis. PDGF-BB, like TPO, showed a significant promoting effect in platelet production (n=5 p= 0.0078) as well as CFU-MK formation (n=5 p=0.0019) compared with the untreated control group. Histology images also indicated that PDGF-BB increased the number of the megakaryocytic cells and its progenitors in bone marrow of irradiated mice. In order to find out the underlying mechanism, we further studied the in vitro effect of PDGF using megakaryocytic cell line M-07e. Our results demonstrated that PDGF alone (100–200ng/ml) significantly activated the PI-3K/AKT signaling pathway (n=9 p=0.014). PDGF plus PI-3K inhibitor (wortmannin, 100nM) was shown to attenuate the expression of AKT (n=9, p=0.0112). Consistently, imatinib mesylate (Gleevec, 1uM) negatively interfered the expression of AKT when combined with PDGF-BB ((n=4, p= 0.0288). PDGF-BB was found to have a similar anti-apoptotic effect as TPO on M07e cells as showed by Annexin V (n=8, p=0.0281), Mitochondrial Membrane Potential (JC-1) (n=7, p=0.0042), and Caspase-3 (n=5, p=0.0080) assays respectively. In summary, our findings showed that PDGF-BB had an in vivo thromobopoietic effect on the radiation induced myelosuppressive mice models. This effect was likely mediated via PDGF receptor with subsequent activation of PI-3K/AKT pathway, which leads to anti-apoptotic effect on megakaryocytes.

scholarly journals Involvement of theca cells and steroids in the regulation of granulosa cell apoptosis in rabbit preovulatory follicles

Reproduction ◽  
2003 ◽  
pp. 709-716 ◽  
Author(s):  
G Maillet ◽  
A Benhaim ◽  
H Mittre ◽  
C Feral
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Rapid Loss ◽  
Theca Cells ◽  
Preovulatory Follicles ◽  
Apoptotic Effect

Follicular atresia is characterized by a rapid loss of granulosa cells and, to a lesser extent, theca cells, via apoptosis. The aim of this study was to investigate the possible involvement of theca cell secretions in the regulation of apoptosis of rabbit granulosa cells. The annexin-V binding method based on externalization of phosphatidylserine to the outer layer of plasma membrane during apoptosis was used to detect apoptotic granulosa cells in flow cytometry. Regulation of apoptosis of granulosa cells was studied in three different culture systems: (i) isolated cultured granulosa cells, (ii) granulosa cells obtained from cultured preovulatory follicles and (iii) granulosa cells co-cultured with theca cells. The results of this study indicate that: (i) the rate of apoptosis of granulosa cells was significantly reduced when granulosa cells were co-cultured with theca cells or obtained from cultured preovulatory follicles in comparison with isolated cultured granulosa cells; (ii) FSH exerts its anti-apoptotic effect only on granulosa cells issued from cultured preovulatory follicles; (iii) ovarian steroids do not affect the percentage of isolated apoptotic granulosa cells; and (iv) the occurrence of an apoptotic process in rabbit theca cells could be upregulated in vitro by hCG and an analogue of the gonadotrophin second messenger cAMP. The results of this study indicate that in rabbits (i) steroids were ineffective in vitro in protecting isolated granulosa cells against apoptosis in comparison with observations in vivo in rats, and (ii) the presence of theca cells was efficient to reduce granulosa cell apoptosis but not sufficient to allow the anti-apoptotic effect of gonadotrophins observed in cultured follicles.

scholarly journals The Antitumor Effect of Lipophilic Bisphosphonate BPH1222 in Melanoma Models: The Role of the PI3K/Akt Pathway and the Small G Protein Rheb

2019 ◽  
Vol 20 (19) ◽  
pp. 4917 ◽  
Author(s):  
Rittler ◽  
Baranyi ◽  
Molnár ◽  
Garay ◽  
Jalsovszky ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Pi3k Pathway ◽  
Recent Success ◽  
Apoptotic Effect ◽  
Cancer Types ◽  
Novel Treatment Strategies ◽  
In Vivo Growth

Malignant melanoma is one of the most metastatic cancer types, and despite recent success with novel treatment strategies, there is still a group of patients who do not respond to any therapies. Earlier, the prenylation inhibitor hydrophilic bisphosphonate zoledronic acid (ZA) was found to inhibit melanoma growth in vitro, but only a weaker effect was observed in vivo due to its hydrophilic properties. Recently, lipophilic bisphosphonates (such as BPH1222) were developed. Accordingly, for the first time, we compared the effect of BPH1222 to ZA in eight melanoma lines using viability, cell-cycle, clonogenic and spheroid assays, videomicroscopy, immunoblot, and xenograft experiments. Based on 2D and spheroid assays, the majority of cell lines were more sensitive to BPH. The activation of Akt and S6 proteins, but not Erk, was inhibited by BPH. Additionally, BPH had a stronger apoptotic effect than ZA, and the changes of Rheb showed a correlation with apoptosis. In vitro, only M24met cells were more sensitive to ZA than to BPH; however, in vivo growth of M24met was inhibited more strongly by BPH. Here, we present that lipophilic BPH is more effective on melanoma cells than ZA and identify the PI3K pathway, particularly Rheb as an important mediator of growth inhibition.

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