Hydrogen peroxide induces apoptotic-like cell death in Microcystis aeruginosa (Chroococcales, Cyanobacteria) in a dose-dependent manner

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.

Download Full-text

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

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.022 ◽

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.

Download Full-text

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

Cancers ◽

10.3390/cancers12123641 ◽

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.

Download Full-text

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

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2018.144 ◽

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.

Download Full-text

Biomarker for Benzopyrene Exposure Is Mitochondrial Mass and Mitochondrial DNA Copy in Blood Cells and Hematopoietic Tissues

Blood ◽

10.1182/blood.v118.21.4889.4889 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4889-4889

Author(s):

Myung-Geun Shin ◽

Hye-Ran Kim ◽

Hyun-Jung Choi ◽

Hwan-Young Kim ◽

Dong-Kyun Han ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Mitochondrial Dna ◽

Peripheral Blood ◽

Blood Cells ◽

Copy Number ◽

Leukemia Cells ◽

Dependent Manner ◽

Mtdna Copy Number ◽

Mitochondrial Mass ◽

Dose Dependent

Abstract Abstract 4889 Benzopyrenes are well known pollutants and carcinogens. They can intercalate into DNA and interfere transcriptions, resulting in causing various human diseases. However, biomarkers of benzopyrene toxicity have not been comprehensively studied in blood and leukemia cells. The current study was investigated to discover biomarkers for benzopyrene exposure in blood cells and leukemia cell lines. Peripheral blood, peripheral blood hematopoietic stem cell and leukemia cells (THP-1, K562, Molt-4 and HL-60) were cultured in RPMI 1640 media with adding 0, 50, 100 and 200μM of benzopyrene. Viability and apoptosis were assessed by tryptophan blue dye exclusion test and flowcytometry using annexin V. Hydrogen peroxide was measured using enzyme immunoassay. Mitochondrial mass, membrane potential and mitochondrial DNA (mtDNA) copy number were measured using MitoTracker Green, Red probes and real time PCR, respectively. The number of cell remained constant for three weeks culture. Viability of four cell lines disclosed significant decrease after two weeks of benzopyrene treatment. Apoptosis was increased in time- and dose-dependent manner after two weeks of benzopyrene treatment. Mitochondrial contents and membrane potentials were dramatically increased in three-week culture at dose dependent manner. Hydrogen peroxide level was significantly elevated after two weeks treatment of benzopyrene compared to non-benzopyrene treatment group. The number of mtDNA copy increased gradually after exposure to benzopyrene. These results indicated that increased mitochondrial mass and mtDNA copy number were biomarkers for direct exposure of benzopyrene in blood cells and hematopoietic tissues. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/687958 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 6

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.

Download Full-text

Streptococcus oralis Induces Lysosomal Impairment of Macrophages via Bacterial Hydrogen Peroxide

Infection and Immunity ◽

10.1128/iai.00134-16 ◽

2016 ◽

Vol 84 (7) ◽

pp. 2042-2050 ◽

Cited By ~ 6

Author(s):

Nobuo Okahashi ◽

Masanobu Nakata ◽

Hirotaka Kuwata ◽

Shigetada Kawabata

Keyword(s):

Hydrogen Peroxide ◽

Cell Death ◽

Cathepsin B ◽

Opportunistic Infections ◽

Specific Inhibitor ◽

Fluorescent Labeling ◽

Dependent Manner ◽

Content Type ◽

Acridine Orange Staining ◽

Streptococcus Oralis

Streptococcus oralis, an oral commensal, belongs to the mitis group of streptococci and occasionally causes opportunistic infections, such as bacterial endocarditis and bacteremia. Recently, we found that the hydrogen peroxide (H2O2) produced byS. oralisis sufficient to kill human monocytes and epithelial cells, implying that streptococcal H2O2is a cytotoxin. In the present study, we investigated whether streptococcal H2O2impacts lysosomes, organelles of the intracellular digestive system, in relation to cell death.S. oralisinfection induced the death of RAW 264 macrophages in an H2O2-dependent manner, which was exemplified by the fact that exogenous H2O2also induced cell death. Infection with either a mutant lackingspxB, which encodes pyruvate oxidase responsible for H2O2production, orStreptococcus mutans, which does not produce H2O2, showed less cytotoxicity. Visualization of lysosomes with LysoTracker revealed lysosome deacidification after infection withS. oralisor exposure to H2O2, which was corroborated by acridine orange staining. Similarly, fluorescent labeling of lysosome-associated membrane protein-1 gradually disappeared during infection withS. oralisor exposure to H2O2. The deacidification and the following induction of cell death were inhibited by chelating iron in lysosomes. Moreover, fluorescent staining of cathepsin B indicated lysosomal destruction. However, treatment of infected cells with a specific inhibitor of cathepsin B had negligible effects on cell death; instead, it suppressed the detachment of dead cells from the culture plates. These results suggest that streptococcal H2O2induces cell death with lysosomal destruction and then the released lysosomal cathepsins contribute to the detachment of the dead cells.

Download Full-text