scholarly journals The effect of temozolomide on Hsp60 and Hsp70 expression in extracellular vesicles derived from U87MG glioma cells

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murat Pekmez ◽  
Cansu Kılcı
Keyword(s):  
Cell Motility ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Glioma Cells ◽  
Hsp70 Expression ◽  
Dependent Manner ◽  
Intracellular Hsp70 ◽  
And Migration ◽  
Shock Proteins ◽  
New Evidence

Abstract Objectives Temozolomide (TMZ) is an effective drug for glioblastoma multiforme (GBM), but the mechanism underlying TMZ resistance is poorly understood. New evidence has revealed that the release of heat shock proteins (Hsps) derived from extracellular vesicles (EVs) play an important role in cancer progression by modulating tumor microenvironment and cellular cross-talk. This study aims to evaluate the effects of TMZ on the expression of EV-derived and cellular Hsps and cell motility in U87MG human glioblastoma cell line. Methods Glial-EVs were isolated from the culture medium and characterized by SEM and immunoblotting. The effect of TMZ treatments (25, 200 and 750 µM) on cell proliferation (MTT assay), migration (scratch assay), and Hsp60 and Hsp70 levels (immunoblotting) were evaluated. Results TMZ treatments led to an increase in intracellular Hsp70 while decreasing EV-derived Hsp70. Cellular Hsp60 level was elevated at the low dose of TMZ, but it reduced at higher TMZ concentrations. Hsp60 was also decreased in EVs secreted from TMZ-treated cells. Besides, TMZ treatment reduced the proliferation and migration of glioma cells in a dose-dependent manner. Conclusions Our results suggest that TMZ has the potential to target both EV-derived and cellular Hsps for GBM treatment, thus it may reduce cell motility.

Scutellarin combined with Lidocaine: a new combination of anti-glioma drugs

2021 ◽  
Author(s):  
Xiu-Ying He ◽  
Xiao-Ming Zhao ◽  
Qing-Jie Xia ◽  
Lei Zhou ◽  
Ting-Hua Wang
Keyword(s):  
Glioma Cells ◽  
Cell Counting ◽  
New Combination ◽  
Dependent Manner ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Migration Ability ◽  
Egfr Expression ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Glioma is the most common primary intracranial tumors. Although great achievements in the treatment have been made, the efficacy is still not satisfactory, which imposes a great burden on patients and society. Therefore, the exploration of new and effective anti-glioma drugs is urgent. Methods Human glioma cells U251 and LN229 cells were included in the study. The proliferation was detected by cell counting kit-8, plate clone formation assay, EdU incorporation assay and xCELLigence real-time cell analyzer. The cell apoptosis was evaluated by TUNEL assay and flow cytometry. The transwell assay was for assessing the migration. Moreover, Western blot was performed to detect the protein level of Epidermal growth factor receptor (EGFR). Results In present study, we found that Scutellarin(SCU) and Lidocaine suppressed the proliferation and migration, and induced the apoptosis of human glioma cells, including U251 and LN229 cells, in a dose-dependent manner. Moreover, the combination of Scutellarin and Lidocaine further restrained the proliferation and migration ability of U251 and LN229 cells, while induced their apoptosis. Mechanistically, the effect of Scutellarin and its combination with Lidocaine on glioma cells was partially associated with the downregulation of EGFR protein. Conclusions Scutellarin and Lidocaine exert a synergistic effect on suppressing the proliferation and migration and induce the apoptosis of glioma cells partly via repressing the EGFR expression.

scholarly journals CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

2018 ◽  
Author(s):  
Koran S. Harris ◽  
Lihong Shi ◽  
Brittni M. Foster ◽  
Mary E. Mobley ◽  
Phyllis L. Elliott ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Kinase Inhibitors ◽  
Marker Gene ◽  
Dependent Manner ◽  
Tumor Initiation ◽  
Cancer Aggressiveness ◽  
Tki Resistance ◽  
And Migration

ABSTRACTCancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used LNCaP-C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.

scholarly journals The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

2015 ◽  
Vol 37 (4) ◽  
pp. 1390-1406 ◽  
Author(s):  
Mei-Han Huang ◽  
Yan-Ming Huang ◽  
Sheng-Nan Wu
Keyword(s):  
Cancer Cells ◽  
Single Channel ◽  
Glioma Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
And Migration ◽  
Ikca Channel ◽  
K Currents

Oxaliplatin (OXAL) is a third-generation organoplatinum which is effective against advanced cancer cells including glioma cells. How this agent and other related compounds interacts with ion channels in glioma cells is poorly understood. OXAL (100 µM) suppressed the amplitude of whole-cell K+ currents (IK); and, either DCEBIO or ionomycin significantly reversed OXAL-mediated inhibition of IK in human 13-06-MG glioma cells. In OXAL-treated cells, TRAM-34 did not suppress IK amplitude in these cells. The intermediate-conductance Ca2+-activated K+ (IKCa) channels subject to activation by DCEBIO and to inhibition by TRAM-34 or clotrimazole were functionally expressed in these cells. Unlike cisplatin, OXAL decreased the probability of IKCa-channel openings in a concentration-dependent manner with an IC50 value of 67 µM. No significant change in single-channel conductance of IKCa channels in the presence of OXAL was demonstrated. Neither large-conductance Ca2+-activated K+ channels nor inwardly rectifying K+ currents in these cells were affected in the presence of OXAL. OXAL also suppressed the proliferation and migration of 13-06-MG cells in a concentration- and time-dependent manner. OXAL reduced IKCa-channel activity in LoVo colorectal cancer cells. Taken together, the inhibition by OXAL of IKCa channels would conceivably be an important mechanism through which it acts on the functional activities of glioma cells occurring in vivo.

scholarly journals FASN Is a Biomarker Enriched in Malignant Glioma-Derived Extracellular Vesicles

2020 ◽  
Vol 21 (6) ◽  
pp. 1931
Author(s):  
Franz L. Ricklefs ◽  
Cecile L. Maire ◽  
Jakob Matschke ◽  
Lasse Dührsen ◽  
Thomas Sauvigny ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Fatty Acid Synthase ◽  
Unmet Need ◽  
Glioma Cells ◽  
Analytical Sensitivity ◽  
Plasma Samples ◽  
Glioma Patient ◽  
Malignant Glioma Cells

Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.

scholarly journals HSP70 Multi-Functionality in Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 587 ◽  
Author(s):  
Zarema Albakova ◽  
Grigoriy A. Armeev ◽  
Leonid M. Kanevskiy ◽  
Elena I. Kovalenko ◽  
Alexander M. Sapozhnikov
Keyword(s):  
Cancer Progression ◽  
Selective Advantage ◽  
Hsp70 Expression ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Cancer Hallmarks ◽  
Anti Cancer ◽  
Apoptotic Pathways ◽  
Senescence Program ◽  
Shock Proteins

The 70-kDa heat shock proteins (HSP70s) are abundantly present in cancer, providing malignant cells selective advantage by suppressing multiple apoptotic pathways, regulating necrosis, bypassing cellular senescence program, interfering with tumor immunity, promoting angiogenesis and supporting metastasis. This direct involvement of HSP70 in most of the cancer hallmarks explains the phenomenon of cancer “addiction” to HSP70, tightly linking tumor survival and growth to the HSP70 expression. HSP70 operates in different states through its catalytic cycle, suggesting that it can multi-function in malignant cells in any of these states. Clinically, tumor cells intensively release HSP70 in extracellular microenvironment, resulting in diverse outcomes for patient survival. Given its clinical significance, small molecule inhibitors were developed to target different sites of the HSP70 machinery. Furthermore, several HSP70-based immunotherapy approaches were assessed in clinical trials. This review will explore different roles of HSP70 on cancer progression and emphasize the importance of understanding the flexibility of HSP70 nature for future development of anti-cancer therapies.

scholarly journals Schisandrin B Inhibits Cell Viability and Migration, and Induces Cell Apoptosis by circ_0009112/miR-708-5p Axis Through PI3K/AKT Pathway in Osteosarcoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Bing Wang ◽  
Xiaowei Wang ◽  
Xing Tong ◽  
Yingang Zhang
Keyword(s):  
Cell Viability ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Akt Pathway ◽  
Schisandrin B ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
U2os Cells ◽  
And Migration

Osteosarcoma is a primary tumor of bone and its incidence is increasing. Schisandrin B (Sch B), a generally used lignan in Chinese medicine, has been found to repress cancer progression. This study aims to reveal the effects and regulatory mechanism of Sch B in the viability, apoptosis and migration of osteosarcoma cells. In this study, we found circ_0009112 expression was higher and miR-708-5p expression was lower in SaOS2 and U2OS cells than in hFOB1.19 cells. Circ_0009112 expression was downregulated, but miR-708-5p was upregulated by Sch B treatment in a dose-dependent manner in SaOS2 and U2OS cells. Sch B exposure inhibited osteosarcoma development in vitro and in vivo; however, these effects were restored by circ_0009112. Furthermore, circ_0009112 acted as a sponge of miR-708-5p. Circ_0009112 regulated PI3K/AKT pathway after Sch B treatment by associating with miR-708-5p. Sch B exposure inhibited cell viability and migration, whereas promoted cell apoptosis by regulating circ_0009112/miR-708-5p axis through PI3K/AKT pathway in osteosarcoma cells. This study provided a theoretical basis for further studying osteosarcoma therapy with Sch B.

scholarly journals The Aryl Hydrocarbon Receptor Is Expressed in Thyroid Carcinoma and Appears to Mediate Epithelial-Mesenchymal-Transition

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 145 ◽  
Author(s):  
Sonia Moretti ◽  
Nicole Nucci ◽  
Elisa Menicali ◽  
Silvia Morelli ◽  
Vittorio Bini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Motility ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Receptor Activation ◽  
Mesenchymal Transition ◽  
Aryl Hydrocarbon ◽  
And Migration

Aryl hydrocarbon receptor (AhR) is expected to promote initiation, progression and invasion of cancer cells regulating proliferation, differentiation, gene expression, inflammation, cell motility and migration. Furthermore, an immunosuppressant function of AhR has been recognized. This study evaluated AhR expression and its role in thyroid cancer progression. AhR expression was assessed by qPCR in 107 thyroid cancer samples (90 PTCs, 11 MTCs, 6 ATCs), and by immunohistochemistry in 41 PTCs. To estimate receptor activation, the expression of target genes CYP1A1 and CYP1B1 was measured. AhR functional effects were evaluated in kynurenine-stimulated FTC-133 and BcPap cell lines by analyzing the expression of genes involved in EMT and cell motility. AhR mRNA expression resulted significantly higher in all the analyzed thyroid cancer samples compared to normal thyroid and a statistically significant correlation with CYP1B1 was detected. Kynurenine-stimulated FTC-133 and BcPap showed the activation of a specific AhR-driven EMT program characterized by E-cadherin decrease and SLUG, N-cadherin and fibronectin increase, resulting in boost of cell motility and invasion. This study confirmed the importance of the IDO1-Kyn-AhR pathway in thyroid cancer tumorigenesis, suggesting an AhR pivotal role in mediating an immunosuppressive microenvironment and favoring the acquisition of a mesenchymal phenotype that could promote invasiveness and metastasis.

Effect of Glioma Stem Cells-derived Extracellular Vesicles on Glucose Metabolism Reprogramming in Glioma via the miR-26a/KLF4/PI3K/Akt axis

2021 ◽  
Author(s):  
Jiaoying Jia ◽  
Yong Peng ◽  
Ming Wang ◽  
Wenjia Ma ◽  
Min Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lactic Acid ◽  
Glucose Metabolism ◽  
Extracellular Vesicles ◽  
Glioma Cells ◽  
Akt Pathway ◽  
Glioma Stem Cells ◽  
Atp Production ◽  
Invasion And Migration ◽  
And Migration

Abstract BackgroundGlioma represents one of the most intractable malignancy occurring in central nervous system. Glioma stem cells (GSCs) constitute a type of seed cells with self-renewal and multi-directional differentiation potentials. This study investigated the mechanism of GSCs-derived extracellular vesicles (EVs) in glucose metabolism reprogramming in glioma.MethodsGlioma cells were treated with different concentrations (10, 20 and 30 μg/mL) of GSCs-EVs. Glucose consumption and lactic acid and adenosine triphosphate (ATP) production were measured and expressions of key enzymes in glycolysis pathway (PFK1, HK2 and PKM2) were detected. The proliferation, invasion and migration of glioma cells were measured. miR-26a expression in GSCs-EVs-treated cells was detected. The targeting relationship between miR-26a and KLF4 was predicted and verified. The phosphorylation levels of PI3K and Akt were detected. Glioma cells were co-incubated with GSCs-EVs and pcDNA-KLF4 to verify the role of PI3K/Akt pathway in glucose metabolism reprogramming.ResultsGlucose consumption and lactic acid and ATP production were promoted, and expressions of PFK1, HK2 and PKM2 were increased in GSCs-EVs-treated cells. GSCs-EVs facilitated proliferation, invasion and migration of glioma cells. miR-26a expression was enhanced in GSCs-EVs-treated cells. GSCs-EVs carried miR-26a into glioma cells and promoted glucose metabolism reprogramming. miR-26a inhibitor reduced the promoting effect of GSCs-EVs on glucose metabolism reprogramming. miR-26a repressed KLF4 expression and activated the PI3K/Akt pathway in glioma cells.ConclusionmiR-26a carried by GSCs-EVs promoted glucose metabolism reprogramming in glioma via targeting KLF4 and activating the PI3K/Akt pathway. This study may offer new insights for targeted intervention of glioma.

scholarly journals Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Constanze Buhrmann ◽  
Ajaikumar B. Kunnumakkara ◽  
Aviral Kumar ◽  
Marek Samec ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Curcuma Longa ◽  
Fibroblast Cells ◽  
Dependent Manner ◽  
Ki 67 ◽  
Concentration Dependent Manner ◽  
Proinflammatory Mediators ◽  
And Migration ◽  
Hct116 Cells

BackgroundTumor microenvironment (TME) provides the essential prerequisite niche for promoting cancer progression and metastasis. Calebin A, a component of Curcuma longa, has long been investigated as a safe multitargeted agent with antitumor and anti-inflammatory properties. However, the multicellular-TME-induced malignancy and the antitumorigenic potential of Calebin A on colorectal cancer (CRC) cells in 3D-alginate cultures are not yet understood, and more in-depth research is needed.Methods3D-alginate tumor cultures (HCT116 cells) in the multicellular proinflammatory TME (fibroblast cells/T lymphocytes), tumor necrosis factor beta (TNF-β)-TME (fibroblast cells/TNF-β) were treated with/without Calebin A to address the pleiotropic actions of Calebin A in the CRC.ResultsWe found that Calebin A downmodulated proliferation, vitality, and migration of HCT116 cells in 3D-alginate cultures in multicellular proinflammatory TME or TNF-β-TME. In addition, Calebin A suppressed TNF-β-, similar to multicellular-TME-induced phosphorylation of nuclear factor kappa B (NF-κB) in a concentration-dependent manner. NF-κB-promoting proinflammatory mediators, associated with tumor growth and antiapoptotic molecules (i.e.,MMP-9, CXCR4, Ki-67, β1-integrin, and Caspase-3) and its translocation to the nucleus in HCT116 cells, were increased in both TME cultures. The multicellular-TME cultures further induced the survival of cancer stem cells (CSCs) (upregulation of CD133, CD44, and ALDH1). Last but not the least, Calebin A suppressed multicellular-, similar to TNF-β-TME-induced rigorous upregulation of NF-κB phosphorylation, various NF-κB-regulated gene products, CSCs activation, and survival in 3D-alginate tumor cultures.ConclusionsThe downmodulation of multicellular proinflammatory-, similar to TNF-β-TME-induced CRC proliferation, survival, and migration by the multitargeting agent Calebin A could be a new therapeutic strategy to suppress inflammation and CRC tumorigenesis.

scholarly journals CD117/c-kit defines a prostate CSC-like subpopulation driving progression and TKI resistance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koran S. Harris ◽  
Lihong Shi ◽  
Brittni M. Foster ◽  
Mary E. Mobley ◽  
Phyllis L. Elliott ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Kinase Inhibitors ◽  
Marker Gene ◽  
Dependent Manner ◽  
Tumor Initiation ◽  
Cancer Aggressiveness ◽  
Tki Resistance ◽  
And Migration

AbstractCancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.

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