scholarly journals Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 427 ◽  
Author(s):  
Aleksandra Szwed ◽  
Katarzyna Miłowska ◽  
Sylwia Michlewska ◽  
Silvia Moreno ◽  
Dzmitry Shcharbin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Line ◽  
Mitochondrial Membrane Potential ◽  
Cancer Cell ◽  
Mitochondrial Membrane ◽  
Cancer Cell Line ◽  
Cns Disorders ◽  
Anti Cancer ◽  
Per Se ◽  
The Impact

Dendrimers as drug carriers can be utilized for drugs and siRNA delivery in central nervous system (CNS) disorders, including various types of cancers, such as neuroblastomas and gliomas. They have also been considered as drugs per se, for example as anti-Alzheimer’s disease (AD), anti-cancer, anti-prion or anti-inflammatory agents. Since the influence of carbosilane–viologen–phosphorus dendrimers (SMT1 and SMT2) on the basic cellular processes of nerve cells had not been investigated, we examined the impact of two generations of these hybrid macromolecules on two murine cell lines—cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). We examined alterations in cellular responses including the activity of mitochondrial dehydrogenases, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, and morphological modifications and fractions of apoptotic and dead cells. Our results show that both dendrimers at low concentrations affected the cancer cell line more than the normal one. Also, generation-dependent effects were found: the highest generation induced greater cytotoxic effects and morphological modifications. The most promising is that the changes in mitochondrial membrane potential and transmission electron microscopy (TEM) images indicate that dendrimer SMT1 can reach mitochondria. Thus, SMT1 and SMT2 seem to have potential as nanocarriers to mitochondria or anti-cancer drugs per se in CNS disorders.

Anaerobic respiration sustains mitochondrial membrane potential in a prolyl hydroxylase pathway-activated cancer cell line in a hypoxic microenvironment

2014 ◽  
Vol 306 (4) ◽  
pp. C334-C342 ◽  
Author(s):  
Eiji Takahashi ◽  
Michihiko Sato
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Cell Line ◽  
Mitochondrial Membrane Potential ◽  
Cancer Cell ◽  
Mitochondrial Membrane ◽  
Cancer Cell Line ◽  
Prolyl Hydroxylase ◽  
Complex Ii ◽  
Pathway Activation

To elucidate how tumor cells produce energy in oxygen-depleted microenvironments, we studied the possibility of mitochondrial electron transport without oxygen. We produced well-controlled oxygen gradients (ΔO2) in monolayer-cultured cells. We then visualized oxygen levels and mitochondrial membrane potential (ΔΦm) in individual cells by using the red shift of green fluorescent protein (GFP) fluorescence and a cationic fluorescent dye, respectively. In this two-dimensional tissue model, ΔΦm was abolished in cells >500 μm from the oxygen source [the anoxic front (AF)], indicating limitations in diffusional oxygen delivery. This result perfectly matched GFP-determined ΔO2. In cells pretreated with dimethyloxaloylglycine (DMOG), a prolyl hydroxylase domain-containing protein (PHD) inhibitor, the AF was expanded to 1,500–2,000 μm from the source. In these cells, tissue ΔO2 was substantially decreased, indicating that PHD pathway activation suppressed mitochondrial respiration. The expansion of the AF and the reduction of ΔO2 were much more prominent in a cancer cell line (Hep3B) than in the equivalent fibroblast-like cell line (COS-7). Hence, the results indicate that PHD pathway-activated cells can sustain ΔΦm, despite significantly decreased electron flux to complex IV. Complex II inhibition abolished the effect of DMOG in expanding the AF, although tissue ΔO2 remained shallow. Separate experiments demonstrated that complex II plays a substantial role in sustaining ΔΦm in DMOG-pretreated Hep3B cells with complex III inhibition. From these results, we conclude that PHD pathway activation can sustain ΔΦm in an otherwise anoxic microenvironment by decreasing tissue ΔO2 while activating oxygen-independent electron transport in mitochondria.

scholarly journals The Antiproliferative and Apoptotic Effects of Capsaicin on an Oral Squamous Cancer Cell Line of Asian Origin, ORL-48

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 322 ◽  
Author(s):  
Mohammad Firdaus Kamaruddin ◽  
Mohammad Zakir Hossain ◽  
Aied Mohamed Alabsi ◽  
Marina Mohd Bakri
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Oral Cancer ◽  
Fluorescence Microscopy ◽  
Cell Line ◽  
Cancer Cell ◽  
Mitochondrial Membrane ◽  
Cancer Cell Line ◽  
Asian Origin ◽  
Cycle Arrest

Background and Objectives: The antitumor activities of capsaicin on various types of cancer cell lines have been reported but the effect of capsaicin on oral cancer, which is prevalent among Asians, are very limited. Thus, this study aimed to investigate the effects of capsaicin on ORL-48, an oral cancer cell line of Asian origin. Materials and Methods: Morphological changes of the ORL-48 cells treated with capsaicin were analyzed using fluorescence microscopy. The apoptotic-inducing activity of capsaicin was further confirmed by Annexin V-Fluorescein isothiocyanate / Propidium iodide (V-FITC/PI) staining using flow cytometry. In order to establish the pathway of apoptosis triggered by the compound on ORL-48 cells, caspase activity was determined and the mitochondrial pathway was verified by mitochondrial membrane potential (MMP) assay. Cell cycle analysis was also performed to identify the cell cycle phase of ORL-48 cells being inhibited by the capsaicin compound. Results: Fluorescence microscopy exhibited the presence of apoptotic features in capsaicin-treated ORL-48 cells. Apoptosis of capsaicin-treated ORL-48 cells revealed disruption of the mitochondrial-membrane potential, activation of caspase-3, -7 and -9 through an intrinsic apoptotic pathway and subsequently, apoptotic DNA fragmentation. The cell cycle arrest occurred in the G1-phase, confirming antiproliferative effect of capsaicin in a time-dependent manner. Conclusion: This study demonstrated that capsaicin is cytotoxic against ORL-48 cells and induces apoptosis in ORL-48 cells possibly through mitochondria mediated intrinsic pathway resulting in cell cycle arrest.

scholarly journals Gondomono (Hedycium spicatum) Ethanol Exstract Anti-Proliferation, Apoptosis and P53 Cancer Cell Line

2021 ◽  
Vol 5 (5) ◽  
pp. 163-169
Author(s):  
Nur Rahman
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Cancer Cell ◽  
P53 Protein ◽  
Cancer Cell Line ◽  
Tumor Cell Line ◽  
Gas Chromatography Mass Spectrometry ◽  
Unhealthy Lifestyle ◽  
Anti Cancer ◽  
The Impact

The incidence of cancer from year to year continues to increase. Some of the causes of this incident include an unhealthy lifestyle, smoking, a diet high in fat and low in fiber. The Gondomono plant (Hedychium spicatum) are the most studied species. Interesting compounds have been identified like coronarin D, which possesses antibacterial, antifungal and antitumor activities, as well as isocoronarin D, linalool and villosin that exhibit better cytotoxicity towards tumor cell lines than the reference compounds used, with villosin not affecting the non-tumor cell line. This study aims to obtain scientific evidence that Gondomono extract (Hedychium spicatum) is proven to be anti-cancer. The impact obtained will be utilized by local Indonesian plants that can be processed or produced as functional food and herbal medicine for anti-cancer bioactivity toxicity with various tests including the making gondomono (Hedycium spicatum) flour, ethanol extraction method, insilico analysis and Gas Chromatography-Mass Spectrometry (GC-MS) analysis, then the second stage test, namely the MTT test, P53 test and apoptosis test. The research design was experimental. Gondomono extract when compared to anticancer ingredients was indeed very far away, gondomono extract was starting to be able to act as apoptosis, it requires a fairly high concentration, from 200 to 400 ppm. As conclusion, the higher the dose of gondomono extract, the higher the expression of p53 protein, the higher. Gondomono extract as a cancer cell killer requires a minimum dose of 368.51 ppm. Keywords: gondomono; Hedycium spicatum; anti-proliferasi; cancer cell line

Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7

2018 ◽  
Vol 18 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Zahra Shahsavari ◽  
Fatemeh Karami-Tehrani ◽  
Siamak Salami
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Membrane Potential ◽  
Cell Line ◽  
Mitochondrial Membrane Potential ◽  
Breast Cancer Cell Line ◽  
Mitochondrial Membrane ◽  
Cancer Cell Line ◽  
Mcf 7

Background: Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer. Objective: Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7. Methods: In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells. Results: Necroptosis and apoptosis have been occurred by Shikonin, with a significant increase in RIPK1 and RIPK3 expressions, although necroptosis was the major rout in MCF-7 cells. Shikonin significantly increased the percentage of the cells in sub-G1 and also those in the later stages of cell cycle, which represents an increase in necroptosis and apoptosis. Under caspase inhibition by Z-VAD-FMK, Shikonin has stimulated necroptosis, which could be arrested by Nec-1. An increase in ROS levels and a decrease in the mitochondrial membrane potential have also been observed. Conclusion: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.

scholarly journals Seeding of breast cancer cell line (MDA-MB-231LUC+) to the mandible induces overexpression of substance P and CGRP throughout the trigeminal ganglion and widespread peripheral sensory neuropathy throughout all three of its divisions

2021 ◽  
Vol 17 ◽  
pp. 174480692110240
Author(s):  
Silvia Gutierrez ◽  
James C Eisenach ◽  
M Danilo Boada
Keyword(s):  
Breast Cancer ◽  
Substance P ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Trigeminal Ganglion ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
The Impact

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.

Depolarized Mitochondrial Membrane Potential and Protection with Duroquinone in Isolated Perfused Lungs from Rats Exposed to Hyperoxia

2021 ◽  
Author(s):  
Said H. Audi ◽  
Swetha Ganesh ◽  
Pardis Taheri ◽  
Xiao Zhang ◽  
Ranjan K. Dash ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Rhodamine 6G ◽  
Computational Approach ◽  
Experimental Protocol ◽  
Perfusion System ◽  
The Impact ◽  
Mitochondrial Uncoupler

Dissipation of mitochondrial membrane potential (Δψm) is a hallmark of mitochondrial dysfunction. our objective was to use a previously developed experimental-computational approach to estimate tissue Δψm in intact lungs of rats exposed to hyperoxia, and to evaluate the ability of duroquinone (DQ) to reverse any hyperoxia-induced depolarization of lung Δψm. Rats were exposed to hyperoxia (>95% O2) or normoxia (room air) for 48 hrs, after which lungs were excised and connected to a ventilation-perfusion system. The experimental protocol consisted of measuring the concentration of the fluorescent dye rhodamine 6G (R6G) during three single-pass phases: loading, washing, and uncoupling, in which the lungs were perfused with and without R6G, and with the mitochondrial uncoupler FCCP, respectively. For normoxic lungs, the protocol was repeated with 1) rotenone (complex I inhibitor), 2) rotenone and either DQ or its vehicle (DMSO), and 3) rotenone, glutathione (GSH), and either DQ or DMSO added to the perfusate. Hyperoxic lungs were studied with and without DQ and GSH added to the perfusate. Computational modeling was used to estimate lung Δψm from R6G data. Rat exposure to hyperoxia resulted in partial depolarization (-33 mV) of lung Δψm, and complex I inhibition depolarized lung Δψm by -83 mV. Results also demonstrate the efficacy of DQ to fully reverse both rotenone-induced and hyperoxia-induced lung Δψm depolarization. This study demonstrates hyperoxia-induced Δψm depolarization in intact lungs, and the utility of this approach for assessing the impact of potential therapies such as exogenous quinones that target mitochondria in intact lungs.

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