scholarly journals Ceramide-induced cell death/survival in murine osteoblasts

2010 ◽  
Vol 206 (2) ◽  
pp. 225-233 ◽  
Author(s):  
P A Hill ◽  
A Tumber
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cell Types ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Diphenyl Tetrazolium Bromide ◽  
General Protein ◽  
Pkc Ζ ◽  
Cell Suicide

Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. We determined whether ceramide treatment contributes to reduced cell viability and increased PCD in primary osteoblasts and the signalling pathways that are involved. Cell viability was determined by the 3-(4,5-dimethyl-thiozol-2-yl)-2,5-diphenyl tetrazolium bromide assay. We found that C2-ceramide (≤10−7 M) promoted osteoblast viability, whilst concentrations ≥2×10−6 M significantly reduced osteoblast viability in a dose- and time-dependent manner. The effect of ceramide on cell viability was specific since C2-dihydroceramide had no effect. Increasing intracellular ceramide levels with either sphingomyelinase (SMase) or an inhibitor of ceramide metabolism also increased osteoblast apoptosis. Ceramide-induced PCD in osteoblasts was determined by nuclear appearance and DNA fragmentation. PCD was induced by both C2-ceramide and SMase. The ability of ceramide (5×10−8 M) to promote osteoblast survival was prevented by a general protein kinase C (PKC) inhibitor and by a PKC ζ inhibitor, whilst osteoblast survival was enhanced in the presence of a protein phosphatase 1 (PP1) inhibitor. Phosphatidylinositol-3 kinase (PI3K) inhibitors had no effect on osteoblast survival. The ability of ceramide (5×10−5 M) to induce apoptosis was prevented by the inhibitors of PP1 and PKC δ, whilst the general PKC and PI3K inhibitors had no effect on it. Our findings suggest that ceramide signals osteoblast survival and apoptosis through different intracellular pathways, and that alteration in the intracellular levels of ceramide may play an important role in bone remodelling.

scholarly journals Participation of PI3K and atypical PKC in Na+-K+-pump stimulation by IGF-I in VSMC

1999 ◽  
Vol 276 (6) ◽  
pp. H2109-H2116 ◽  
Author(s):  
Dailin Li ◽  
Gary Sweeney ◽  
Qinghua Wang ◽  
Amira Klip
Keyword(s):  
Kinase Inhibitor ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Atypical Pkc ◽  
Kinase C ◽  
Igf I ◽  
Pump Activity ◽  
Pkc Ζ ◽  
Dose Dependent

The activity of the Na+-K+-pump is intricately linked to the maintenance of vascular tone. Here we demonstrate that insulin-like growth factor I (IGF-I) increases Na+-K+-pump activity in the vascular smooth muscle cell (VSMC) clone A7r5 in a time- and dose-dependent manner. This stimulatory effect of IGF-I was prevented by the tyrosine kinase inhibitor genistein (5 μM) and by the specific phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin (100 nM) and LY-294002 (25 μM). IGF-I activated a wortmannin-sensitive PI3K and its purported effector, the atypical protein kinase C (PKC)-ζ. Stimulation of PKC-ζ was prevented by the generic PKC inhibitor GF109203x (bisindolylmaleimide, 10 μM). Downregulation of diacylglycerol-sensitive (conventional and novel) PKCs by 24-h pretreatment with 1 μM phorbol 12-myristate 13-acetate had no effect on IGF-I-stimulated Na+-K+-pump activity. Similarly, inhibition of only conventional and novel PKCs with GF109203x (1 μM) had no effect on IGF-I-stimulated Na+-K+-pump activity. In contrast, a concentration of GF109203x (10 μM) that also inhibits the atypical PKCs abolished Na+-K+-pump stimulation by IGF-I. Neither the Na+-K+-2Cl−cotransporter inhibitor bumetanide (100 μM) nor the Na+/H+exchanger inhibitor HOE-694 (5 μM) affected the Na+-K+-pump stimulation by IGF-I, suggesting that a rise in intracellular Na+ concentration is not necessary for increased Na+-K+-pump activity. These results suggest that IGF-I directly stimulates the Na+-K+pump via a signaling pathway involving PI3K and atypical PKC (ζ).

scholarly journals Pyrrolizidine Alkaloids Induce Cell Death in Human HepaRG Cells in a Structure-Dependent Manner

2020 ◽  
Vol 22 (1) ◽  
pp. 202
Author(s):  
Josephin Glück ◽  
Julia Waizenegger ◽  
Albert Braeuning ◽  
Stefanie Hessel-Pras
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Pyrrolizidine Alkaloids ◽  
Defense Mechanism ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma Cell

Pyrrolizidine alkaloids (PAs) are a group of secondary metabolites produced in various plant species as a defense mechanism against herbivores. PAs consist of a necine base, which is esterified with one or two necine acids. Humans are exposed to PAs by consumption of contaminated food. PA intoxication in humans causes acute and chronic hepatotoxicity. It is considered that enzymatic PA toxification in hepatocytes is structure-dependent. In this study, we aimed to elucidate the induction of PA-induced cell death associated with apoptosis activation. Therefore, 22 structurally different PAs were analyzed concerning the disturbance of cell viability in the metabolically competent human hepatoma cell line HepaRG. The chosen PAs represent the main necine base structures and the different esterification types. Open-chained and cyclic heliotridine- and retronecine-type diesters induced strong cytotoxic effects, while treatment of HepaRG with monoesters did not affect cell viability. For more detailed investigation of apoptosis induction, comprising caspase activation and gene expression analysis, 14 PA representatives were selected. The proapoptotic effects were in line with the potency observed in cell viability studies. In vitro data point towards a strong structure–activity relationship whose effectiveness needs to be investigated in vivo and can then be the basis for a structure-associated risk assessment.

Abstract 346: Lipophilic Statins Attenuate Human Atrial Fibroblast Viability In Vitro

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kiranjit K Sran ◽  
Yun Li ◽  
Saeid Ghavami ◽  
Melanie Ngo ◽  
Rakesh C Arora ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Heart Surgery ◽  
Cardiac Fibrosis ◽  
Therapeutic Option ◽  
Open Heart Surgery ◽  
Myocardial Cell ◽  
Dependent Manner ◽  
Vitro Effect

Cardiovascular diseases (CVD) leading to heart failure are associated with myocardial cell loss and cardiac fibrosis. Hydroxymethylglutaryl-Coenzyme-A Reductase (HMGR) inhibitors ("statins") are widely used to limit cardiovascular events in patients with hypercholesterolemia and CVD by altering their lipid profile. HMGR inhibition reduces cholesterol precursor L-mevalonate production, whose depletion induces autophagy, apoptosis, and endoplasmic reticulum stress in various cell types. However it is unclear if this is a class effect or a phenomenon specific to various compounds. We examined the in vitro effect of HMGR inhibition on human atrial fibroblast (hATF) viability with particular reference to hydrophilic vs lipophilic compounds. Hypothesis- Lipophilic statins induce cell death in primary hATF via mevalonate depletion; whereas hydrophilic statins do not have any effect on hATF viability. IRB approval was obtained for collection of hATF from consenting patients undergoing open heart surgery. Cells were treated with atorvastatin, simvastatin or pravastatin (0.1, 1.0 or 10 λM) for 24, 48, 72 or 96 hours. Expression of proteins involved in the regulation of apoptosis and autophagy was assessed using immunoblotting. Cell viability was assessed using MTT assay. Treatment of hATF with 0.1 - 10 λM atorvastatin or simvastatin (lipophilic statins) resulted in progressively reduced cell viability in time and dose-dependent manner. Viability could be rescued by coincubation with mevalonate. Expression of key apoptotic cascade proteins -Bcl2, Bax and cleaved Caspase3 showed a clear induction of apoptosis. Also, there was an increase in Atg5-12 expression at 24h indicating induction of early autophagic response. Pravastatin (hydrophilic statin) did not affect cell viability or autophagy and apoptosis. We conclude that statin-induced cell death is mediated by mevalonate depletion, which activates intrinsic apoptotic pathways in hATF. Lipophilic statins impair the viability of hATFs in vitro, whereas hydrophilic statins have no effect on cell growth and cell viability of hATFs. This may represent an additional pleiotropic effect of statins, and may represent a novel therapeutic option for the prevention and treatment of cardiac fibrosis.

scholarly journals Activation of Phosphatidylinositol 3-Kinase Contributes to Insulin-Like Growth Factor I-Mediated Inhibition of Pancreatic β-Cell Death

Endocrinology ◽  
2002 ◽  
Vol 143 (10) ◽  
pp. 3802-3812 ◽  
Author(s):  
Wenli Liu ◽  
Catherine Chin-Chance ◽  
Eun-Jig Lee ◽  
William L. Lowe
Keyword(s):  
Cell Death ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Cell Types ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Β Cell ◽  
Creb Phosphorylation ◽  
Lactate Dehydrogenase Release ◽  
Igf I

Abstract To begin to determine whether IGF-I treatment represents a potential means of enhancing the survival of islet cell grafts after transplantation, the present studies established a model of β-cell death secondary to loss of trophic support and examined the ability of IGF-I to prevent cell death. The studies were performed using the rat pancreatic β-cell line, INS-1. Incubating INS-1 cells in RPMI 1640 and 0.25% BSA for 48 h increased cell death, as determined by lactate dehydrogenase release, compared with that of cells maintained in RPMI and 10% fetal calf serum. Addition of 100 ng/ml IGF-I to the serum-free medium decreased lactate dehydrogenase release to a level comparable to that found in cells maintained in fetal calf serum. Similar results were seen using a mouse β-cell line, MIN6, infected with an adenovirus expressing IGF-I. Examination of IGF-I-stimulated signaling demonstrated that IGF-I increased the phosphorylation of protein kinase B in both cell lines, whereas IGF-I-induced phosphorylation of the MAPKs, ERK1 and -2, was observed only in INS-1 cells. The effect of IGF-I on phosphorylation of substrates of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B was also examined in INS-1 cells. IGF-I increased the phosphorylation of glycogen synthase kinase 3β, BAD, FKHR, and p70S6 kinase. Another pathway that has been shown to mediate the protective of IGF-I in some cell types is activation of cAMP response element-binding protein (CREB). IGF-I increased CREB phosphorylation at a concentration as low as 10 ng/ml, and this effect was inhibited by H89, a PKA inhibitor, and PD98059, a MAPK kinase inhibitor. Consistent with the effect of IGF-I on CREB phosphorylation, IGF-I increased the transcriptional activity of CREB, although it had no effect on CREB binding to DNA. Use of inhibitors of the PI 3-kinase (LY 294002) or ERK (PD98059) pathways or CREB phosphorylation (H89) in the cell death assay demonstrated partial abrogation of the protective effect of IGF-I with LY 294002. These data demonstrate that IGF-I protects pancreatic β-cells from cell death secondary to loss of trophic support and that, although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in β-cells.

scholarly journals Comparative Assessment of the Volatile Profile, Antioxidant Capacity and Cytotoxic Potential of Different Preparation of Millefolli Herba Samples

2001 ◽  
Vol 71 (3) ◽  
pp. 69-78
Author(s):  
Mihaela Buleandra ◽  
Zenovia Moldovan ◽  
Irinel Adriana Badea ◽  
Iulia Gabriela David ◽  
Dana Elena Popa ◽  
...  
Keyword(s):  
Cell Death ◽  
Essential Oil ◽  
Cell Viability ◽  
Antioxidant Capacity ◽  
Apoptotic Cell ◽  
Principal Component ◽  
Volatile Components ◽  
Dependent Manner ◽  
Hydroalcoholic Extract ◽  
Hct 116

Millefolii herba is an available product on the Romanian market as mixture of stems, leaves and flowers of Achillea millefolium L. There were established its volatile compounds profile, total polyphenolic content (TPC), antioxidant capacity and effects on HCT 116 cell viability and programmed cell death. The infusion, hydroalcoholic extract and hydrodistillated essential oil were studied. A comparative analysis using static headspace (HS) and hydro-distillation (HD) GC/MS of the volatile components from Millefolii herba was realized: the essential oil contains chamazulene as the principal component (37.1%), while 1,8-cineole (46.8%) is the main constituent of headspace volatiles. The highest antioxidant capacity was found in essential oil, compared with hydroalcoholic extract, infusion and ascorbic acid. Yarrow hydroalcoholic extract reduced the HCT 116 cell viability and induced the apoptotic cell death in a dose and time dependent manner.

scholarly journals Chemical Hybridization of Sulfasalazine and Dihydroartemisinin Promotes Brain Tumor Cell Death 

2021 ◽  
Author(s):  
Annemarie Ackermann ◽  
Aysun Çapcı ◽  
Michael Buchfelder ◽  
Svetlana Tsogoeva ◽  
Nicolai Savaskan
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Malignant Tumors ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
Dependent Manner ◽  
Tumor Cell Death ◽  
Brain Tumor Cell ◽  
Combinational Treatment ◽  
The Impact

Abstract Gliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds to add or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized covalently bound hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA) called AC254. In previous studies both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of sole SAS and DHA, their 1:1 combination and as a chemical linked hybrid (AC254) on rodent and human glioma cells. In our study SAS showed no or only a mild effect on glioma whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinatorial treatment of both parent substances in most used concentrations. In addition to its reduction in cell viability and induction of cell death the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to provide new chemotherapeutic drugs.

scholarly journals Benzo(a)pyrene, an Active Product of Cigarette Smoke, Role in PLA2 Isoforms Activation in Colon Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 193s-193s
Author(s):  
S. Sharma ◽  
S. Yadav ◽  
S. Rana ◽  
P. Avti ◽  
K.L. Khanduja
Keyword(s):  
Colon Cancer ◽  
Cell Viability ◽  
Cigarette Smoke ◽  
Membrane Integrity ◽  
Annexin V ◽  
Cell Types ◽  
Ros Generation ◽  
Dependent Manner ◽  
Colon Cells ◽  
Ht 29

Background and aim: One of the active combustion product of cigarette smoke, Benzo[a]pyrenes, role in pulmonary cancer is clearly understood. However, its role in gastrointestinal cancer including colon cancer is not clearly understood. Methods: In this study, benzo(a)pyrenes was treated to colon cells to evaluate its role in cell viability, cellular ROS, and gene expression of various PLA2 isoforms was evaluated by FACS and PCR. The identified PLA2 was silenced at the gene level to evaluate its role in cell viability and ROS generation. Results: B(a)P treatment at 1 µg/mL for 48 h to HCT-15 male colon cells significantly reduced the cell viability without affecting HT-29 female colon cells. Higher doses and longer treatment duration with B(a)P showed that female colon cells were highly sensitive than male colon cells. Annexin-V/PI staining for preapoptotic detection showed that B(a)P treatment increased the apoptosis in both the cell types in a concentration and time-dependent manner. The cytosolic ROS (cROS) and superoxide radical (SOR) formation in the female colon cells was significantly higher than male colon cells unlike the mitochondrial ROS (mtROS) production which was significantly higher in male colon cells. Treatment with B(a)P significantly upregulated the IID and IVA PLA2 isoform groups in HCT-15 male colon cells, whereas IB was upregulated in HT-29 female colon cells among the various PLA2 isozyme gene studied (IB, IID, III, IVA, IVB, IVC, VI, X, aiPLA2 and iPLA2). Gene silencing experiments targeting PLA2 IID and IVA in the HCT-15 male colon cells and IB in HT-29 female colon cells showed no effect with B(a)P treatment on the cell proliferation, apoptosis, membrane integrity and free radicals (ROS, mtROS, and SOR) generation. Conclusion: Targeting specific PLA2 isozymes in a cell-specific manner abolished the B(a)P-induced PLA2-mediated oxidative damage–related signaling pathways.

scholarly journals Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Annemarie Ackermann ◽  
Aysun Çapcı ◽  
Michael Buchfelder ◽  
Svetlana B. Tsogoeva ◽  
Nicolai Savaskan
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Viability ◽  
Malignant Tumors ◽  
Glioma Cells ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Tumor Cell Death ◽  
Combinational Treatment ◽  
The Impact

AbstractGliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.

Unfolded Protein Response is Involved in Trans-Platinum (II) Complex-Induced Apoptosis in Prostate Cancer Cells via ROS Accumulation

2019 ◽  
Vol 19 (9) ◽  
pp. 1184-1195
Author(s):  
Didem Karakas ◽  
Buse Cevatemre ◽  
Arzu Y. Oral ◽  
Veysel T. Yilmaz ◽  
Engin Ulukaya
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Viability ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Treatment Modalities ◽  
Drug Candidate ◽  
Ros Generation ◽  
Dependent Manner

Background:Prostate cancer is one of the most common cancer types and it is the sixth leading cause of cancer-related death in men worldwide. Even though novel treatment modalities have been developed, it still a lifethreatening disease. Therefore novel compounds are needed to improve the overall survival.Methods:In our study, it was aimed to evaluate the anti-cancer activity of newly synthesized Platinum (II) [Pt(II)] complex on DU145, LNCaP and PC-3 prostate cancer cell lines. The cytotoxic activity of Pt(II) complex was tested by SRB and ATP cell viability assays. To detect the mode of cell death; fluorescent staining, flow cytometry and western blot analyses were performed.Results:The Pt(II) complex treatment resulted in a decrease in cell viability and increasing levels of apoptotic markers (pyknotic nuclei, annexin-V, caspase 3/7 activity) and a decrease in mitochondrial membrane potential in a dose dependent manner. Among cell types, tested PC-3 cells were found to be more sensitive to Pt(II) complex, demonstrating elevation of DNA damage in this cell line. In addition, Pt(II) complex induced Endoplasmic Reticulum (ER) stress by triggering ROS generation. More importantly, pre-treatment with NAC alleviated Pt(II) complex-mediated ER stress and cell death in PC-3.Conclusion:These findings suggest an upstream role of ROS production in Pt(II) complex-induced ER stressmediated apoptotic cell death. Considering the ROS-mediated apoptosis inducing the effect of Pt(II) complex, it warrants further evaluation as a novel metal-containing anticancer drug candidate.

Specific Cytostatic and Cytotoxic Effect of Dihydrochelerythrine in Glioblastoma Cells: Role of NF-κB/β-catenin and STAT3/IL-6 Pathways

2019 ◽  
Vol 18 (10) ◽  
pp. 1386-1393 ◽  
Author(s):  
Tereza C.C. Silva ◽  
Giselle P. de Faria Lopes ◽  
Noélio de J. Menezes-Filho ◽  
Diêgo M. de Oliveira ◽  
Ezequiel Pereira ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Annexin V ◽  
Experimental Models ◽  
Blue Dye ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
U251 Cell ◽  
U251 Cells

Background: A glioblastoma is a primary CNS tumor that is more aggressive and lethal than other brain tumors. Its location, rapid proliferation, invasive growth, angiogenesis and immunosuppression are the main factors that limit its treatment, making it a major challenge to neuro-oncology. Objective: This study investigated the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell death and β-catenin, NFκB, STAT3/pSTAT3 and interleukins roles. Method: In vitro experimental models of human (U251 and GL-15) and murine (C6) glioblastoma cells were cultured in the presence of DHC at increasing concentrations for MTT assay and exclusion trypan blue dye to determine EC50. Afterward, C6 and U251 cells were treated with 100 µM DHC or DMSO 0.1% for cell cycle, annexin and expression of β-catenin/NFκB/STAT3/pSTAT3 by flow cytometry or immunofluorescence. Interleukin quantification was made by Cytometric Bead Array. Results: A significant decrease was observed in C6 and U251 cell viability in a time and dose-dependent manner. GL-15 cell viability decreased only when treated with 200 µM DHC. This maximum concentration affected neither astrocytes nor microglia viability. A cytostatic effect of DHC was observed in C6 and U251 cells after 48 h of 100 µM DHC treatment. After 72 h of DHC treatment, C6 presented 80% of annexin-V+ cells compared to 10% of annexin-V+ U251 cells. C6 cells demonstrated significant high levels of NFκ B and β-catenin cytoplasmic fraction. Additionally, DHC treatment resulted in higher significant levels of IL-6 than did other interleukins and STAT3 up-regulation in U251 cells. Conclusion: These results demonstrate that DHC acts as a chemosensitizing agent selective for glioma cells not affecting non-tumor cells. Considering tumor heterogeneity, DHC demonstrated an anti-cancer potential to activate different cell death pathways. DHC demonstrated could be used for chemotherapy and immunotherapy applications in glioblastomas in the future.

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