scholarly journals In vitro activity of 1H-phenalen-1-one derivatives against Leishmania spp. and evidence of programmed cell death

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Atteneri López-Arencibia ◽  
María Reyes-Batlle ◽  
Mónica B. Freijo ◽  
Ines Sifaoui ◽  
Carlos J. Bethencourt-Estrella ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Programmed Cell Death ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Chromatin Condensation ◽  
Death Process ◽  
Leishmania Spp ◽  
Characteristic Features

Abstract Background The in vitro activity against Leishmania spp. of a novel group of compounds, phenalenone derivatives, is described in this study. Previous studies have shown that some phenalenones present leishmanicidal activity, and induce a decrease in the mitochondrial membrane potential in L. amazonensis parasites, so in order to elucidate the evidence of programmed cell death occurring inside the promastigote stage, different assays were performed in two different species of Leishmania. Methods We focused on the determination of the programmed cell death evidence by detecting the characteristic features of the apoptosis-like process, such as phosphatidylserine exposure, mitochondrial membrane potential, and chromatin condensation among others. Results The results showed that four molecules activated the apoptosis-like process in the parasite. All the signals observed were indicative of the death process that the parasites were undergoing. Conclusions The present results highlight the potential use of phenalenone derivatives against Leishmania species and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

Anti-Glycophorin C Induces a Loss of Mitochondrial Membrane Potential but Fails To Activate Apoptotic Caspases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4097-4097
Author(s):  
Gregory A. Denomme ◽  
Jonathan Micieli ◽  
Jenny Shu ◽  
Dan Wang ◽  
Bernard J. Fernandes
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Growth Inhibition ◽  
Mitochondrial Membrane Potential ◽  
K562 Cell ◽  
Mitochondrial Membrane ◽  
K562 Cells ◽  
Suppressive Effect ◽  
Glycophorin C

Abstract The human erythrocyte transmembrane sialoglycoprotein, glycophorin C (GYPC), plays a functional role in regulating red cell shape and mechanical stability. Antibodies to GYPC cause hemolytic disease of the fetus and newborn (HDFN) that is associated with classical Fcγ receptor-mediated phagocytosis. However, in vitro clonogenic studies with cord blood progenitor cells suggest that anti-GYPC also suppresses erythropoiesis, which is consistent with the observations of severe and early fetal anemia and late onset neonatal anemia [Transfus Med2005;15:125–32]. The mechanism of the suppressive effect on erythropoiesis is unknown. The K562 erythroleukemic cell line treated with anti-GYPC is a potential model system to study the suppressive effect of anti-GYPC. The present in vitro studies were designed to confirm the effect of anti-GYPC on K562 cell growth and viability, and to evaluate changes in mitochondrial membrane potential, phosphatidylserine (PS) expression, propidium iodide (PI) binding, and caspase activation. K562 cells fail to grow in the presence of anti-GYPC confirming earlier CFU-E/BFU-E studies [Brit J Haematol2006;133:443–4], and increased the exofacial expression of PS/PI over time. This process was caspase-independent as demonstrated by the failure of Z-VAD, a caspase inhibitor, to reverse growth inhibition and PS/PI expression. A loss of mitochondrial membrane potential was demonstrated using JC-1, a cationic dye that is sensitive to potential-dependent accumulation or loss in mitochondria. There was a 50% increase in K562 cell mitochondrial membrane potential disruption after 2 days of culture with anti-GYPC (see figure). Morphological examination of May Grunwalde Giemsa-stained K562 cells treated with anti-GYPC for 2 days showed a decrease in mitotic activity compared to isotype treated cells. By day 4, the anti-GYPC treated cells were showing evidence of plasma membrane damage and cell death resulting from fragmentation and dissolution of the cytoplasm. The addition of hemin, an oxidative form of iron protoporphyrin IX known to induce erythroid differentiation of K562 cells, to anti-GYPC treated cells reversed growth inhibition by 45% but did not prevent the loss of mitochondrial membrane potential. Overall, although caspases appear to be unimportant in anti-GYPC induced cell death, the mitchondria play an important role as the early events leading to antibody-mediated suppression of erythropoiesis. Mitochondrial Membrane Potential Disruption by Anti-GYPC Mitochondrial Membrane Potential Disruption by Anti-GYPC

In vitro effects of triterpenic acids from olive leaf extracts on the mitochondrial membrane potential of promastigote stage of Leishmania spp

Phytomedicine ◽  
2014 ◽  
Vol 21 (12) ◽  
pp. 1689-1694 ◽  
Author(s):  
Ines Sifaoui ◽  
Atteneri López-Arencibia ◽  
Carmen Mª Martín-Navarro ◽  
Juan Carlos Ticona ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Olive Leaf ◽  
Leaf Extracts ◽  
Triterpenic Acids ◽  
Leishmania Spp ◽  
In Vitro Effects

scholarly journals Biocontrol of collar rot on passion fruits via induction of apoptosis in the collar rot pathogen by Bacillus subtilis

2020 ◽  
Author(s):  
Yu-Hsuan Chen ◽  
Pei-Chun Lee ◽  
Tzu-Pi Huang
Keyword(s):  
Cell Death ◽  
Bacillus Subtilis ◽  
Membrane Potential ◽  
Energy Metabolism ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Chromatin Condensation ◽  
Passion Fruit ◽  
Biocontrol Agents ◽  
Collar Rot

The seedlings and fresh fruits of passion fruits are of high value in local and global trade. Fusarium solani is a main disease-causing agents affecting passion fruits. The objectives were to develop Bacillus-based biocontrol agents for the management of fusarium diseases on passion fruits and to investigate their putative control mechanisms. Our studies indicated Bacillus subtilis YBC and 151B1 showed antagonistic activity to F. solani PF7 from passion fruits and inhibited the conidial germination of strain PF7. The application of broth cultures from B. subtilis 151B1 and YBC in SYB medium reduced disease severity of fusarium wilt on the leaves of passion fruits, and enhanced the survival rates of passion fruit seedlings challenged with F. solani PF7. With regard to the putative mechanisms of disease control, the results indicated the treatments consisting of the respective culture filtrates from B. subtilis 151B1 and YBC broths caused aberrant conidial morphology and the loss of cell membrane integrity. Additionally, the treatments caused reductions in mitochondrial membrane potential and interfered with the energy metabolism of F. solani PF7. The treatments also enhanced reactive oxygen species accumulation, and resulted in the externalization of phosphatidylserine, chromatin condensation, and DNA fragmentation, suggesting their functions in triggering apoptotic-like cell death. In conclusion, B. subtilis 151B1 and YBC are potential biocontrol agents for passion fruit disease caused by F. solani. Their control efficacy may result from the produced surfactins to trigger apoptotic-like cell death, reducing the mitochondrial membrane potential and interfering with the energy metabolism of the pathogen.

scholarly journals Geranylgeranyl Acetone Prevents Glutamate-induced Cell Death in HT-22 Cells by Increasing Mitochondrial Membrane Potential

2020 ◽  
Author(s):  
Eriko Sugano ◽  
Yuka Endo ◽  
Akihisa Sugai ◽  
Yuki Kikuchi ◽  
Kitako Tabata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Oxygen Species ◽  
Mouse Hippocampus ◽  
Calcium Buffering ◽  
Shock Proteins

Geranylgeranyl acetone (GGA) protects against various types of cell damages by upregulating heat shock proteins. We investigated whether GGA protect neuronal cells from cell death induced by oxidative stress. Glutamate exposure was lethal to HT-22 cells which comprise a neuronal line derived from mouse hippocampus. This configuration is often used as a model for hippocampus neurodegeneration in vitro. In the present study, GGA protected HT-22 cells from glutamate-induced oxidative stress. GGA pretreatment did not induce Hsps. Moreover, reactive oxygen species increased to the same extent in both GGA-pretreated and untreated cells exposed to glutamate. In contrast, glutamate exposure and GGA pretreatment increased mitochondrial membrane potential. However, increases in intracellular Ca2+ concentration were inhibited by GGA pretreatment. In addition, the increase of phosphorylated ERKs by the glutamate exposure was inhibited by GGA pretreatment. These findings suggest that GGA protects HT-22 cells from glutamate-provoked cell death without Hsp induction and that the mitochondrial calcium buffering capacity plays an important role in this protective effect.

scholarly journals Cyclometalated Iridium(III) Complex–Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular Ca2+ Overload from the Endoplasmic Reticulum and a Decrease in Mitochondrial Membrane Potential

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7028
Author(s):  
Chandrasekar Balachandran ◽  
Kenta Yokoi ◽  
Kana Naito ◽  
Jebiti Haribabu ◽  
Yuichi Tamura ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Mitochondrial Membrane Potential ◽  
Intracellular Signaling ◽  
Mitochondrial Membrane ◽  
Jurkat Cells ◽  
Mechanistic Study

In our previous paper, we reported that amphiphilic Ir complex–peptide hybrids (IPHs) containing basic peptides such as KK(K)GG (K: lysine, G: glycine) (e.g., ASb-2) exhibited potent anticancer activity against Jurkat cells, with the dead cells showing a strong green emission. Our initial mechanistic studies of this cell death suggest that IPHs would bind to the calcium (Ca2+)–calmodulin (CaM) complex and induce an overload of intracellular Ca2+, resulting in the induction of non-apoptotic programmed cell death. In this work, we conduct a detailed mechanistic study of cell death induced by ASb-2, a typical example of IPHs, and describe how ASb-2 induces paraptotic programmed cell death in a manner similar to that of celastrol, a naturally occurring triterpenoid that is known to function as a paraptosis inducer in cancer cells. It is suggested that ASb-2 (50 µM) induces ER stress and decreases the mitochondrial membrane potential (ΔΨm), thus triggering intracellular signaling pathways and resulting in cytoplasmic vacuolization in Jurkat cells (which is a typical phenomenon of paraptosis), while the change in ΔΨm values is negligibly induced by celastrol and curcumin. Other experimental data imply that both ASb-2 and celastrol induce paraptotic cell death in Jurkat cells, but this induction occurs via different signaling pathways.

scholarly journals Calcium Delivery by Electroporation Induces In Vitro Cell Death through Mitochondrial Dysfunction without DNA Damages

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 425 ◽  
Author(s):  
Laure Gibot ◽  
Audrey Montigny ◽  
Houda Baaziz ◽  
Isabelle Fourquaux ◽  
Marc Audebert ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Tumor Growth ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Dermal Fibroblasts ◽  
Atp Depletion ◽  
Secondary Malignancies ◽  
Adolescent Cancer

Adolescent cancer survivors present increased risks of developing secondary malignancies due to cancer therapy. Electrochemotherapy is a promising anti-cancer approach that potentiates the cytotoxic effect of drugs by application of external electric field pulses. Clinicians proposed to associate electroporation and calcium. The current study aims to unravel the toxic mechanisms of calcium electroporation, in particular if calcium presents a genotoxic profile and if its cytotoxicity comes from the ion itself or from osmotic stress. Human dermal fibroblasts and colorectal HCT-116 cell line were treated by electrochemotherapy using bleomycin, cisplatin, calcium, or magnesium. Genotoxicity, cytotoxicity, mitochondrial membrane potential, ATP content, and caspases activities were assessed in cells grown on monolayers and tumor growth was assayed in tumor spheroids. Results in monolayers show that unlike cisplatin and bleomycin, calcium electroporation induces cell death without genotoxicity induction. Its cytotoxicity correlates with a dramatic fall in mitochondrial membrane potential and ATP depletion. Opposite of magnesium, over seven days of calcium electroporation led to spheroid tumor growth regression. As non-genotoxic, calcium has a better safety profile than conventional anticancer drugs. Calcium is already authorized by different health authorities worldwide. Therefore, calcium electroporation should be a cancer treatment of choice due to the reduced potential of secondary malignancies.

scholarly journals Programmed cell death in yeast by thionin-like peptide from Capsicum annuum fruits involving activation of caspases and extracellular H+ flux

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Gabriel B. Taveira ◽  
Érica O. Mello ◽  
Sávio B. Souza ◽  
Renan M. Monteiro ◽  
Alessandro C. Ramos ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Programmed Cell Death ◽  
Cell Surface ◽  
Capsicum Annuum ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Transport Systems ◽  
Ph Homeostasis ◽  
Surface Ph

CaThi is a thionin-like peptide isolated from fruits of Capsicum annuum, which has strong antimicrobial activity against bacteria, yeasts and filamentous fungi, and induced reactive oxygen species (ROS) in fungi. ROS are molecules that appear in the early stages of programmed cell death or apoptosis in fungi. Due to this fact, in this work we analyzed some events that may be related to process of apoptosis on yeast induced by CaThi. To investigate this possibility, we evaluated phosphatidylserine (PS) externalization, presence of active caspases and the ability of CaThi to bind to DNA in Candida tropicalis cells. Additionally, we investigated mitochondrial membrane potential, cell surface pH, and extracellular H+ fluxes in C. tropicalis cells after treatment with CaThi. Our results showed that CaThi induced PS externalization in the outer leaflet of the cell membrane, activation of caspases, and it had the ability for DNA binding and to dissipate mitochondrial membrane potential. In addition, the cell surface pH increased significantly when the C. tropicalis cells were exposed to CaThi which corroborates with ~96% inhibition on extracellular H+ efflux. Taking together, these data suggest that this peptide is capable of promoting an imbalance in pH homeostasis during yeast cell death playing a modulatory role in the H+ transport systems. In conclusion, our results strongly indicated that CaThi triggers apoptosis in C. tropicalis cells, involving a pH signaling mechanism.

scholarly journals Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study

2021 ◽  
Vol 14 (6) ◽  
pp. 552
Author(s):  
Carlos J. Bethencourt-Estrella ◽  
Samuel Delgado-Hernández ◽  
Atteneri López-Arencibia ◽  
Desirée San Nicolás-Hernández ◽  
Ines Sifaoui ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Therapeutic Potential ◽  
Chromatin Condensation ◽  
Protozoan Parasite ◽  
The United States ◽  
Death Process

The neglected infection known as Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, results in more than 7000 deaths per year, with an increasing number of cases in non-endemic areas such as Europe or the United States. Moreover, with the current available therapy, only two compounds which are active against the acute phase of the disease are readily available. In addition, these therapeutic agents display multiple undesired side effects such as high toxicity, they are expensive, the treatment is lengthy and the resistant strain has emerged. Therefore, there is a need to find new compounds against Chagas disease which should be active against the parasite but also cause low toxicity to the patients. In the present work, the activity of novel acrylonitriles against Trypanosoma cruzi was evaluated as well as the analysis of the physiological events induced in the treated parasites related to the cell death process. Hence, the characteristic features of an apoptosis-like process such as chromatin condensation and mitochondrial membrane potential, among others, were studied. From the 32 compounds tested against the epimastigote stage of T. cruzi, 11 were selected based on their selectivity index to determine if these compounds were able to induce programmed cell death (PCD) in the treated parasites. Furthermore, acrylonitriles Q5, Q7, Q19, Q27 and Q29 were shown to trigger physiological events related in the PCD. Therefore, this study highlights the therapeutic potential of acrylonitriles as novel trypanocidal agents.

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