In Vitro Oxidative Activation: A Model for the Cytotoxic Action of 9-Hydroxy Ellipticine Derivatives

1983 ◽  
pp. 149-181 ◽  
Author(s):  
B. Meunier ◽  
C. Auclair ◽  
J. Bernadou ◽  
G. Meunier ◽  
M. Maftouh ◽  
...  
Keyword(s):  
Cytotoxic Action ◽  
Oxidative Activation

scholarly journals Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα

2011 ◽  
Vol 441 (1) ◽  
pp. 189-198 ◽  
Author(s):  
Christine A. McCary ◽  
Youngdae Yoon ◽  
Candace Panagabko ◽  
Wonhwa Cho ◽  
Jeffrey Atkinson ◽  
...  
Keyword(s):  
Vitamin E ◽  
Lipid Vesicles ◽  
C2 Domain ◽  
Binding Studies ◽  
Leucocyte Migration ◽  
Protein Kinase Cα ◽  
Oxidative Activation ◽  
Regulatory Effects ◽  
Opposing Effects

Vitamin E isoforms have opposing regulatory effects on leucocyte recruitment during inflammation. Furthermore, in vitro, vitamin E isoforms have opposing effects on leucocyte migration across endothelial cells by regulating VCAM (vascular cell-adhesion molecule)-1 activation of endothelial cell PKCα (protein kinase Cα). However, it is not known whether tocopherols directly regulate cofactor-dependent or oxidative activation of PKCα. We report in the present paper that cofactor-dependent activation of recombinant PKCα was increased by γ-tocopherol and was inhibited by α-tocopherol. Oxidative activation of PKCα was inhibited by α-tocopherol at a 10-fold lower concentration than γ-tocopherol. In binding studies, NBD (7-nitrobenz-2-oxa-1,3-diazole)-tagged α-tocopherol directly bound to full-length PKCα or the PKCα-C1a domain, but not PKCζ. NBD-tagged α-tocopherol binding to PKCα or the PKCα-C1a domain was blocked by diacylglycerol, α-tocopherol, γ-tocopherol and retinol, but not by cholesterol or PS (phosphatidylserine). Tocopherols enhanced PKCα-C2 domain binding to PS-containing lipid vesicles. In contrast, the PKCα-C2 domain did not bind to lipid vesicles containing tocopherol without PS. The PKCα-C1b domain did not bind to vesicles containing tocopherol and PS. In summary, α-tocopherol and γ-tocopherol bind the diacylglycerol-binding site on PKCα-C1a and can enhance PKCα-C2 binding to PS-containing vesicles. Thus the tocopherols can function as agonists or antagonists for differential regulation of PKCα.

Combined Vitamins B12b and C Induce the Glutathione Depletion and the Death of Epidermoid Human Larynx Carcinoma Cells HEp-2

2000 ◽  
Vol 20 (5) ◽  
pp. 411-417 ◽  
Author(s):  
Vladimir S. Akatov ◽  
Yury V. Evtodienko ◽  
Violetta V. Leshchenko ◽  
Vera V. Teplova ◽  
Margarita M. Potselueva ◽  
...  
Keyword(s):  
Redox System ◽  
Carcinoma Cells ◽  
Glutathione Depletion ◽  
Cytotoxic Action ◽  
Glutathione Level ◽  
Human Larynx ◽  
Combined Action ◽  
Human Larynx Carcinoma ◽  
Preceding Cell

The combination of hydroxocobalamin (vitamin B12b) and ascorbicacid (vitamin C) can cause the death of tumor cells at the concentrationsof the components at which they are nontoxic when administeredseparately. This cytotoxic action on epidermoid human larynx carcinomacells HEp-2 in vitro is shown to be due to the hydrogen peroxidegenerated by the combination of vitamins B12b and C. The drop inthe glutathione level preceding cell death was found to be the result ofcombined action of the vitamins. It is supposed that the induction of celldeath by combined action of vitamins B12b and C is connected to the damageof the cell redox system.

scholarly journals Cytotoxic Activity of Antineoplastic Agents on Fertility: A Systematic Review

2020 ◽  
Vol 42 (11) ◽  
pp. 759-768
Author(s):  
Gabriel Acácio de Moura ◽  
Paula Bruno Monteiro
Keyword(s):  
Antineoplastic Agents ◽  
Site Effect ◽  
Cytotoxic Action ◽  
Long Term Effects ◽  
Treatment Type ◽  
Number Of Patients ◽  
Serum Hormone ◽  
Hormonal Modulation ◽  
Selection Of

Abstract Objective To analyze the long-term effects of antineoplastic treatments on patient fertility. Selection of Studies The studies were selected through the New PubMed, Scielo and Lilacs databases along with references used for the creation of the present work. For the selection of studies, articles published between the periods from January 1, 2015 to April 6, 2020 in the English, Portuguese and Spanish languages were used. As inclusion criteria: cohort studies and studies conducted in vitro. As exclusion criteria: review articles, reported cases, studies that do not address thematic reproduction, studies that do not address the cancer theme, articles that used animals, articles that address the preservation of fertility and articles in duplicate in the bases. Data Collection The collected data included: age of the patient at the beginning of treatment, type of neoplasm, type of antineoplastic treatment, chemotherapy used, radiotherapy dosage, radiotherapy site, effect of antineoplastic agents on fertility and number of patients in the study. Data Synthesis Thirty studies were evaluated, antineoplastic chemotherapy agents and radiotherapy modulate serum hormone levels, reduces germ cell quantities and correlated with an increase in sterility rates. The effects mentioned occur in patients in the prepubertal and postpubertal age. Conclusion Antineoplastic treatments have cytotoxic effects on the germ cells leading to hormonal modulation, and pubertal status does not interfere with the cytotoxic action of therapies.

Endothelial Alterations During The Platelet Activating Factor (PAF) Respiratory Distress Syndrome

1981 ◽  
Author(s):  
J C Lewis ◽  
J T O’Flaherty ◽  
C M McCall ◽  
R L Wykle
Keyword(s):  
Electron Microscopy ◽  
Plasma Membrane ◽  
Platelet Activating Factor ◽  
Capillary Endothelium ◽  
Cytotoxic Action ◽  
High Concentration ◽  
Rabbit Lung ◽  
Capillary Endothelial Cells ◽  
Platelet Aggregates

PAF (l-0-alkyl-2-0-acetyl-sn-gylcero-3-phosphocholine) induces polymorphonucelar leukocyte and platelet stasis in rabbit lung capillaries in vitro and produces a model of acute respiratory disease. Since PAF mediates anaphylactic reactions, a study was done to determine the ultrastructural effects of PAF treatment. Mature rabbits were treated by intravenous administration of either PAF (0.15-10 μg/kg: 8 animals) or BSA (the PAF carrier: 3 animals) prior to sacrifice and intraventricular perfusion with 0.1 M phosphate buffered (pH 7.2) glutaraldehyde (2.5%). Animals (n=5) injected with a high concentration of PAF (3-10 μg/kg) and sacrificed within 15 minutes of PAF administration had grossly contracted lungs, the vasculature of which (as observed by scanning electron microscopy) contained numerous marginated leukocytes and platelet aggregates. Animals (n=3) given PAF in the concentration range 0.15-2.4 μg/kg had less consistent lung contraction and fewer platelet aggregates within capillaries. Luminal surfaces of capillary endothelial cells in all PAF treated animals (when observed by transmission electron microscopy [TEM]) were dramatically altered. In contrast to the uniformly smooth surfaces in control animals, vessels in the PAF treated animals had tortuous surfaces with plasma membrane discontinuities and protrusion of plasma membrane fragments into the capillary lumen. Morphometric analysis of TEM micrographs substantiated statistically significant (p<0.01) increases in the number and size of plasmalemmal vesicles.These observations clearly document a cytotoxic effect for capillary endothelium. This cytotoxic action may in part explain the clinical effect of PAF.

scholarly journals Flower Infusions From Cornus mas and Cornus kousa Inhibit Aldose Reductase Enzyme, Without Any Effects on Lipotoxicity

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091286
Author(s):  
Vladimír Forman ◽  
Ivana Šušaníková ◽  
Ľubica Kukurová ◽  
Emil Švajdlenka ◽  
Milan Nagy ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Cell Model ◽  
Enzyme Reaction ◽  
Fibroblast Cell ◽  
Protective Role ◽  
Blood Levels ◽  
Cytotoxic Action ◽  
Cornus Mas ◽  
Cornus Kousa

Aldose reductase inhibitors are considered to be potential therapeutic agents for chronic diabetic complications. Diabetes mellitus can be accompanied by elevated blood levels of free fatty acids, which can cause lipotoxicity. Herbal extracts and their constituents are promising agents which have the potential for alleviating these complications. Our study was focused on the influence on these effects by flower infusions from Cornus mas L. and Cornus kousa F.Buerger ex Hance. Initially, phenolic compounds were quantified in the dried flowers. Next, we studied the ability of flower infusions from both plants to inhibit aldose reductase in vitro, the protective role in the cell model of lipotoxicity, and the cytotoxic action on fibroblast cell line NIH-3T3 by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium bromide assay. Both species are rich in phenolics; C. kousa flowers contain slightly higher amounts of phenolic acids (20.8%) and flavonoids (56.1%) than C. mas (20.2%) and (47.4%), respectively. Both extracts showed effective inhibition, expressed as half-maximal inhibitory concentration (IC50) (the concentration of inhibitor required to exhibit 50% inhibition of the enzyme reaction), of aldose reductase in non-toxic low concentrations (IC50 = 3.06 μg/mL for C. mas and IC50 = 2.49 μg/mL for C. kousa, respectively). In contrast, these concentrations of both extracts had almost no effects in the lipotoxicity cell model. To our knowledge, this study is the first report on C. mas and C. kousa flowers’ aldose reductase inhibitory activity and influence upon lipotoxicity.

scholarly journals In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues

2020 ◽  
Vol 13 (3) ◽  
pp. 47 ◽  
Author(s):  
Katarzyna B. Kaczor-Keller ◽  
Anna Pawlik ◽  
Jacek Scianowski ◽  
Agata Pacuła ◽  
Magdalena Obieziurska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Biological Activities ◽  
Cytotoxic Action ◽  
Organoselenium Compounds ◽  
M Cell ◽  
Normal Prostate ◽  
Prostate Cell ◽  
Anticancer Mechanism

Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.

scholarly journals Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Li Yang ◽  
MingJing Shen ◽  
Li Jun Xu ◽  
Xiaodong Yang ◽  
Ying Tsai ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Death Receptor ◽  
Neutralizing Antibody ◽  
Erk Signaling ◽  
Cytotoxic Action ◽  
Cell Cytotoxicity ◽  
Nk Cell Cytotoxicity ◽  
Resistant Cells

Abstract Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell’s function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.

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