scholarly journals Antifungal and Anti-Biofilm Effects of Caffeic Acid Phenethyl Ester on Different Candida Species

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1359
Author(s):  
Ibrahim Alfarrayeh ◽  
Edit Pollák ◽  
Árpád Czéh ◽  
András Vida ◽  
Sourav Das ◽  
...  
Keyword(s):  
Cell Death ◽  
Candida Species ◽  
Caffeic Acid Phenethyl Ester ◽  
Dependent Manner ◽  
Cell Shrinkage ◽  
Nuclear Condensation ◽  
Cell Death Response ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Strain Dependent

This study investigated the effect of CAPE on planktonic growth, biofilm-forming abilities, mature biofilms, and cell death of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis strains. Our results showed a strain- and dose-dependent effect of CAPE on Candida, and the MIC values were between 12.5 and 100 µg/mL. Similarly, the MBIC values of CAPE ranging between 50 and 100 µg/mL highlighted the inhibition of the biofilm-forming abilities in a dose-dependent manner, as well. However, CAPE showed a weak to moderate biofilm eradication ability (19-49%) on different Candida strains mature biofilms. Both caspase-dependent and caspase-independent apoptosis after CAPE treatment were observed in certain tested Candida strains. Our study has displayed typical apoptotic hallmarks of CAPE-induced chromatin margination, nuclear blebs, nuclear condensation, plasma membrane detachment, enlarged lysosomes, cytoplasm fragmentation, cell wall distortion, whole-cell shrinkage, and necrosis. In conclusion, CAPE has a concentration and strain-dependent inhibitory activity on viability, biofilm formation ability, and cell death response in the different Candida species.

Inhibition of Thrombin-induced Neuronal Cell Death by Recombinant Thrombomodulin and E5510, a Synthetic Thrombin Receptor Signaling Inhibitor

1999 ◽  
Vol 82 (09) ◽  
pp. 1071-1077 ◽  
Author(s):  
Krishna Pada Sarker ◽  
Kazuhiro Abeyama ◽  
Jun-ichiro Nishi ◽  
Masanori Nakata ◽  
Takeshi Tokioka ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
Thrombin Inhibitors ◽  
Coagulation Cascade ◽  
Thrombin Receptor ◽  
Functional Domain ◽  
Dependent Manner ◽  
Nuclear Condensation ◽  
Human Neuroblastoma ◽  
Recombinant Thrombomodulin

SummaryThrombin, a serine protease generated by the activation of the blood coagulation cascade following vessel injury, converts fibrinogen to fibrin, activates platelets and several coagulation factors, and plays a pivotal role in thrombosis and haemostasis. Thrombin acts as a mitogen and apoptosis inducer in a dose-dependent fashion. We have previously shown that thrombin caused proliferation of vascular smooth muscle cells (VSMCs). Here, we show that a low concentration of thrombin caused proliferation of mouse neuroblastoma (Neuro-2a) and human neuroblastoma (NB-1) cells, while higher concentrations affected cell viability in a time-dependent manner. Similar effects were observed when thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) was applied. The dying cells showed nuclear condensation and fragmentation, suggesting that cell death occurred by apoptosis. The extent to which thrombin induced cell death was significantly attenuated by recombinant thrombomodulin (rTM), or by a minimum functional domain of TM, termed E456. Furthermore, a synthetic compound that inhibits signaling from the thrombin receptor, 4-cyano-5,5-bis (4-methoxyphenyl)-4-pentanoic acid (E5510), and the antioxidant N-acetyl L-cysteine (NAC), efficiently prevented thrombin-induced Neuro-2a cell death. Thus, thrombin inhibitors and antioxidant appear to neutralize thrombin toxicity.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

scholarly journals Enhanced Malignant Phenotypes of Glioblastoma Cells Surviving NPe6-Mediated Photodynamic Therapy are Regulated via ERK1/2 Activation

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3641
Author(s):  
Tatsuya Kobayashi ◽  
Makoto Miyazaki ◽  
Nobuyoshi Sasaki ◽  
Shun Yamamuro ◽  
Eita Uchida ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Talaporfin Sodium ◽  
Polymerase Inhibitor ◽  
Human Gbm ◽  
Dose Dependent

To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.

scholarly journals OsJAZ13 Negatively Regulates Jasmonate Signaling and Activates Hypersensitive Cell Death Response in Rice

2020 ◽  
Vol 21 (12) ◽  
pp. 4379
Author(s):  
Xiujing Feng ◽  
Lei Zhang ◽  
Xiaoli Wei ◽  
Yun Zhou ◽  
Yan Dai ◽  
...  
Keyword(s):  
Cell Death ◽  
Splice Variants ◽  
Adaptor Protein ◽  
Dependent Manner ◽  
Hypersensitive Cell Death ◽  
Cell Death Response ◽  
Jaz Proteins ◽  
Localization Analysis ◽  
And Function

Jasmonate ZIM-domain (JAZ) proteins belong to the subgroup of TIFY family and act as key regulators of jasmonate (JA) responses in plants. To date, only a few JAZ proteins have been characterized in rice. Here, we report the identification and function of rice OsJAZ13 gene. The gene encodes three different splice variants: OsJAZ13a, OsJAZ13b, and OsJAZ13c. The expression of OsJAZ13 was mainly activated in vegetative tissues and transiently responded to JA and ethylene. Subcellular localization analysis indicated OsJAZ13a is a nuclear protein. Yeast two-hybrid assays revealed OsJAZ13a directly interacts with OsMYC2, and also with OsCOI1, in a COR-dependent manner. Furthermore, OsJAZ13a recruited a general co-repressor OsTPL via an adaptor protein OsNINJA. Remarkably, overexpression of OsJAZ13a resulted in the attenuation of root by methyl JA. Furthermore, OsJAZ13a-overexpressing plants developed lesion mimics in the sheath after approximately 30–45 days of growth. Tillers with necrosis died a few days later. Gene-expression analysis suggested the role of OsJAZ13 in modulating the expression of JA/ethylene response-related genes to regulate growth and activate hypersensitive cell death. Taken together, these observations describe a novel regulatory mechanism in rice and provide the basis for elucidating the function of OsJAZ13 in signal transduction and cell death in plants.

scholarly journals P.042 Raloxifene sensitizes glioblastoma cells to hypoxia-induced death through inhibition of stress granule dissolution

2018 ◽  
Vol 45 (s2) ◽  
pp. S27-S27
Author(s):  
A Robichaud ◽  
K Attwood ◽  
A Balgi ◽  
M Roberge ◽  
A Weeks
Keyword(s):  
Cell Death ◽  
Glioma Cells ◽  
Treatment Resistance ◽  
Cell Counting ◽  
Dependent Manner ◽  
Treatment Results ◽  
Malignant Brain Tumour ◽  
Cytoplasmic Rna ◽  
Dose Dependent ◽  
Tumour Cell Death

Background: Glioblastoma (GBM) is the most common primary malignant brain tumour. Despite aggressive therapy, median survival is only 14 months. Death typically results from treatment failure and local recurrence. The GBM microenvironment is highly hypoxic, which correlates with treatment resistance. Cytoplasmic RNA stress granules (SGs) form in response to hypoxic stress and act as sights of mRNA triage, allowing preferential translation of pro-survival mRNA during stress. We hypothesize that SGs may play a role in hypoxia-induced resistance to therapy, and may be targetable by chemotherapeutics to improve outcomes. Methods: We screened 1280 approved compounds to identify drugs that inhibited formation or dissolution of SGs in U251 glioma cells. Raloxifene inhibited SG dissolution in a dose dependent manner. We treated cells with raloxifene and incubated them in hypoxia, and then measured rates of cell death using cell counting and Presto blue. Results: Cell death rates were synergistically higher in cells treated with the combination of raloxifene and hypoxia compared to either treatment alone. Conclusions: Raloxifene inhibits the dissolution of SGs in glioma cells, and combination treatment results in synergistic tumour cell death. Taken together, this provides evidence that inhibition of SG dissolution may be a viable target for future GBM chemotherapeutics.

scholarly journals Song Bu Li Decoction, a Traditional Uyghur Medicine, Protects Cell Death by Regulation of Oxidative Stress and Differentiation in Cultured PC12 Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Maitinuer Maiwulanjiang ◽  
Kevin Y. Zhu ◽  
Jianping Chen ◽  
Abudureyimu Miernisha ◽  
Sherry L. Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Pc12 Cells ◽  
Stress Proteins ◽  
Antioxidant Response ◽  
Scientific Basis ◽  
Herbal Extract ◽  
Dependent Manner ◽  
Protein Marker ◽  
Dose Dependent

Song Bu Li decoction (SBL) is a traditional Uyghur medicinal herbal preparation, containing Nardostachyos Radix et Rhizoma. Recently, SBL is being used to treat neurological disorders (insomnia and neurasthenia) and heart disorders (arrhythmia and palpitation). Although this herbal extract has been used for many years, there is no scientific basis about its effectiveness. Here, we aimed to evaluate the protective and differentiating activities of SBL in cultured PC12 cells. The pretreatment of SBL protected the cell against tBHP-induced cell death in a dose-dependent manner. In parallel, SBL suppressed intracellular reactive oxygen species (ROS) formation. The transcriptional activity of antioxidant response element (ARE), as well as the key antioxidative stress proteins, was induced in dose-dependent manner by SBL in the cultures. In cultured PC12 cells, the expression of neurofilament, a protein marker for neuronal differentiation, was markedly induced by applied herbal extract. Moreover, the nerve growth factor- (NGF-) induced neurite outgrowth in cultured PC12 cells was significantly potentiated by the cotreatment of SBL. In accord, the expression of neurofilament was increased in the treatment of SBL. These results therefore suggested a possible role of SBL by its effect on neuron differentiation and protection against oxidative stress.

scholarly journals Synthesis, cytotoxicity, apoptosis and cell cycle arrest of a ruthenium multi-substituted Keggin-type polyoxotungstate

2021 ◽  
Author(s):  
Shifang Jia ◽  
Yanzhen Wen ◽  
Xiuli Hao ◽  
Yan Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Cytotoxic Potential ◽  
Cycle Arrest ◽  
Elemental Analyses ◽  
Keggin Anions ◽  
Dose Dependent

Abstract The ruthenium multi-substituted polyoxotungstate with chemical formulae of K7[SiW9O37Ru4(H2O)3Cl3]·15H2O (S1) was synthesized by a conventional aqueous solution containing the trilacunary Keggin-anions β-Na9HSiW9O34·12H2O(S2) and RuCl3·nH2O(S3). Compound S1 was characterized by elemental analyses, EDS, TG analyses, IR, UV/Vis and XPS. The cytotoxic potential of compound S1 was tested on C33A, DLD-1, HepG-2 cancer cells and human normal embryonic lung fibroblasts cell MRC-5. The viability of the treated cells was evaluated by MTT assay. The mode of cell death was assessed by morphological study of DNA damage and apoptosis assays. Compound S1 induced cell death in a dose-dependent manner, and the mode of cell death was essentially apoptosis though necrosis was also noticed. Cell cycle analysis by flow cytometry indicated that compound S1 caused cell cycle arrest and accumulated cells in S phase.

scholarly journals Cannabidiol Induces Apoptosis and Perturbs Mitochondrial Function in Human and Canine Glioma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Chase Gross ◽  
Dominique A. Ramirez ◽  
Stephanie McGrath ◽  
Daniel L. Gustafson
Keyword(s):  
Cell Death ◽  
Anticancer Agent ◽  
Glioma Cells ◽  
Fluorescent Imaging ◽  
Mitochondrial Activity ◽  
Dependent Manner ◽  
Trpv1 Channel ◽  
Pharmacologic Inhibitors ◽  
Dose Dependent

Cannabidiol (CBD), the major non-psychoactive compound found in cannabis, is frequently used both as a nutraceutical and therapeutic. Despite anecdotal evidence as an anticancer agent, little is known about the effect CBD has on cancer cells. Given the intractability and poor prognoses of brain cancers in human and veterinary medicine, we sought to characterize the in vitro cytotoxicity of CBD on human and canine gliomas. Glioma cells treated with CBD showed a range of cytotoxicity from 4.9 to 8.2 μg/ml; canine cells appeared to be more sensitive than human. Treatment with >5 μg/ml CBD invariably produced large cytosolic vesicles. The mode of cell death was then interrogated using pharmacologic inhibitors. Inhibition of apoptosis was sufficient to rescue CBD-mediated cytotoxicity. Inhibition of RIPK3, a classical necroptosis kinase, also rescued cells from death and prevented the formation of the large cytosolic vesicles. Next, cellular mitochondrial activity in the presence of CBD was assessed and within 2 hours of treatment CBD reduced oxygen consumption in a dose dependent manner with almost complete ablation of activity at 10 μg/ml CBD. Fluorescent imaging with a mitochondrial-specific dye revealed that the large cytosolic vesicles were, in fact, swollen mitochondria. Lastly, calcium channels were pharmacologically inhibited and the effect on cell death was determined. Inhibition of mitochondrial channel VDAC1, but not the TRPV1 channel, rescued cells from CBD-mediated cytotoxicity. These results demonstrate the cytotoxic nature of CBD in human and canine glioma cells and suggest a mechanism of action involving dysregulation of calcium homeostasis and mitochondrial activity.

NUCLEAR PROENKEPHALIN INDUCES CELL DEATH IN A P53 DOSE-DEPENDENT MANNER

1996 ◽  
Vol 24 (4) ◽  
pp. 571S-571S
Author(s):  
Deborah A. Dewar ◽  
Carolyn Spraggon ◽  
Carol Midgeley ◽  
David Lane ◽  
Alan Prescott ◽  
...  
Keyword(s):  
Cell Death ◽  
Dependent Manner ◽  
Dose Dependent

In Vitro Activity of a Novel Fully Human Anti-CD40 Antibody CHIR-12.12 in Chronic Lymphocytic Leukemia: Blockade of CD40 Activation and Induction of ADCC.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2504-2504 ◽  
Author(s):  
Xia Tong ◽  
Georgios V. Georgakis ◽  
Long Li ◽  
O’Brien Susan ◽  
Younes Anas ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Line ◽  
Blood Donors ◽  
Lymphocytic Leukemia ◽  
Dependent Manner ◽  
Dose Dependent

Abstract B-cell chronic lymphocytic leukemia (CLL) is characterized by in vivo accumulation of long-lived CD5+ B cells. However when cultured in vitro CLL cells die quickly by apoptosis. Protection from apoptosis in vivo is believed to result from supply of survival signals provided by cells in the microenvironment. We and others have previously reported that CLL cells express CD40 receptor, and that CD40 stimulation of CLL cells may rescue CLL cells from spontaneous and drug-induced apoptosis in vitro. These observations suggested that blocking CD40-CD40L pathway might deprive CLL cells from survival signals and induce apoptosis. To test this hypothesis, we have generated a fully human anti-CD40 blocking monoclonal antibody in XenoMousemice (Abgenix, Inc.). The antibody CHIR-12.12 was first evaluated for its effect on normal human lymphocytes. Lymphocytes from all 10 healthy blood donors did not proliferate in response to CHIR-12.12 at any concentration tested (0.0001 mg/ml to 10 mg/ml range). In contrast, activating CD40 on normal B-lymphocytes by CD40L induced their proliferation in vitro. Importantly, CHIR-12.12 inhibited CD40L- induced proliferation in a dose dependent manner with an average IC50 of 51 ± 26 pM (n=10 blood donors). The antagonistic activity of CHIR-12.12 was then tested in primary CLL samples from 9 patients. CHIR-12.12 alone did not induce CLL cell proliferation. In contrast, primary CLL cells incubated with CD40L, either resisted spontaneous cell death or proliferated. This effect was reversed by co-incubation with CHIR-12.12 antibody, restoring CLL cell death (n=9). CHIR-12.12 was then examined for its ability to lyse CLL cell line EHEB by antibody dependent cell mediated cytotoxicity (ADCC). Freshly isolated human NK cells from normal volunteer blood donors were used as effector cells. CHIR-12.12 showed lysis activity in a dose dependent manner and produced maximum lysis levels at 0.1 mg/ml. When compared with rituximab, CHIR-12.12 mediated greater maximum specific lysis (27.2 % Vs 16.2 %, p= 0.007). The greater ADCC by CHIR-12.12 was not due to higher density of CD40 molecules on CLL cell line compared to CD20 molecules. The CLL target cells expressed 509053 ±13560 CD20 molecules compared to 48416 ± 584 CD40 molecules. Collectively, these preclinical data suggest that CHIR-12.12 monoclonal antibody may have a therapeutic role in patients with CLL.

Sign in / Sign up

Export Citation Format

Share Document