scholarly journals Regucalcin ameliorates Doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria

2021 ◽  
Author(s):  
Noor A Mohammed ◽  
Israa Hakeem ◽  
Nikolas J Hodges ◽  
Francesco Michelangeli
Keyword(s):  
Cell Death ◽  
Cell Model ◽  
Cancer Drug ◽  
Kidney Cells ◽  
Strongly Correlated ◽  
Caspase 9 ◽  
Membrane Blebbing ◽  
Chemically Induced ◽  
Anti Cancer ◽  
Liver And Kidney

Doxorubicin (DOX) is a potent anti-cancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 hours over a range of concentrations and the LC50 was determined to be 7µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 hours, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically-induced cell stress.

scholarly journals Expression of P-170 glycoprotein sensitizes lymphoblastoid CEM cells to mitochondria-mediated apoptosis

2001 ◽  
Vol 355 (3) ◽  
pp. 587-595 ◽  
Author(s):  
Paola MATARRESE ◽  
Ugo TESTA ◽  
Roberto CAUDA ◽  
Stefano VELLA ◽  
Lucrezia GAMBARDELLA ◽  
...  
Keyword(s):  
Cell Death ◽  
Multidrug Resistance ◽  
Cell Line ◽  
Mitochondrial Membrane ◽  
Cell Model ◽  
Cancer Drug ◽  
Type I ◽  
Wild Type ◽  
Membrane Hyperpolarization ◽  
Tnf Α

Multidrug resistance caused by P-glycoprotein (P-170) is a phenomenon by which cells exposed to a single drug acquire resistance to other structurally and functionally unrelated drugs. This is a widespread phenomenon described in vivo in the management of infectious as well as non-infectious diseases. Several in vitro models have been developed in order to evaluate physiopathological properties of P-170. Among these are P-170-expressing variants of the human T-lymphoblastoid CEM cell line called VBL100. As a general rule, drug resistance normally results in resistance to apoptosis induction. By contrast, a paradoxical activity is exerted in this cell model by the cytokine tumour necrosis factor-α (TNF-α), which is capable of inducing apoptosis in P-170-expressing variants better than in wild-type (wt) cells. In the present study we partially address the mechanisms underlying this activity. In fact, the susceptibility of VBL100 cells to TNF-α appears to be specifically due to the depolarization of their mitochondrial membrane, a key factor for apoptotic induction. The same was observed with staurosporine, a specific mitochondrion-mediated proapoptotic chemical probe. Conversely, other proapoptotic stimuli, such as Fas/CD95 or the anti-cancer drug etoposide, did induce significant cell death in wild type cells only. Thus, schematically, mitochondrially dependent stimuli appeared to be more effective in VBL100-cell killing, while ‘physiological’ stimuli showed the opposite behaviour. Importantly, under steady-state conditions, VBL100 cells displayed per se a mitochondrial membrane hyperpolarization that appeared strictly related to their high susceptibility to specific apoptotic stimuli. In conclusion, the study of a well-established cell model such as that represented by the wt/VBL CEM lymphoid cell line seems to suggest that the multidrug resistance phenotype can specifically sensitize cells towards ‘unphysiological’, mitochondria-associated cell death cascade or, in the same fashion, it could shift cells from type I (mainly plasma membrane-associated) towards type II (mainly mitochondrial membrane-associated) phenotype.

scholarly journals Effects of light-activated diazido-Pt IV complexes on cancer cells in vitro

2013 ◽  
Vol 371 (1995) ◽  
pp. 20120118 ◽  
Author(s):  
Patrick J. Bednarski ◽  
Katharina Korpis ◽  
Aron F. Westendorf ◽  
Steffi Perfahl ◽  
Renate Grünert
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Calf Thymus Dna ◽  
Cross Resistance ◽  
Cancer Drug ◽  
Cancer Cell Growth ◽  
Calf Thymus ◽  
Anti Cancer ◽  
Cellular Dna

Various Pt IV diazides have been investigated over the years as light-activatable prodrugs that interfere with cell proliferation, accumulate in cancer cells and cause cell death. The potencies of the complexes vary depending on the substituted amines (pyridine=piperidine>ammine) as well as the coordination geometry ( trans diazide> cis ). Light-activated Pt IV diazides tend to be less specific than cisplatin at inhibiting cancer cell growth, but cells resistant to cisplatin show little cross-resistance to Pt IV diazides. Platinum is accumulated in the cancer cells to a similar level as cisplatin, but only when activated by light, indicating that reactive Pt species form photolytically. Studies show that Pt also becomes attached to cellular DNA upon the light activation of various Pt IV diazides. Structures of some of the photolysis products were elucidated by LC–MS/MS; monoaqua- and diaqua-Pt II complexes form that are reactive towards biomolecules such as calf thymus DNA. Platination of calf thymus DNA can be blocked by the addition of nucleophiles such as glutathione and chloride, further evidence that aqua-Pt II species form upon irradiation. Evidence is presented that reactive oxygen species may be generated in the first hours following photoactivation. Cell death does not take the usual apoptotic pathways seen with cisplatin, but appears to involve autophagy. Thus, photoactivated diazido-Pt IV complexes represent an interesting class of potential anti-cancer agents that can be selectively activated by light and kill cells by a mechanism different to the anti-cancer drug cisplatin.

scholarly journals Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells

2018 ◽  
Vol 92 (4) ◽  
pp. 1507-1524 ◽  
Author(s):  
Harshal Nemade ◽  
Umesh Chaudhari ◽  
Aviseka Acharya ◽  
Jürgen Hescheler ◽  
Jan Georg Hengstler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Pluripotent Stem Cells ◽  
Cancer Drug ◽  
Human Cardiomyocytes ◽  
Anti Cancer ◽  
Cell Death Mechanisms

scholarly journals CB13, a novel PPARγ ligand, overcomes radio-resistance via ROS generation and ER stress in human non-small cell lung cancer

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Tae Woo Kim ◽  
Da-Won Hong ◽  
Sung Hee Hong
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Er Stress ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cancer Drug ◽  
Small Cell Lung ◽  
Pparγ Agonist ◽  
Anti Cancer

Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-known therapeutic target for type 2 diabetes as well as is a potential target for effective anti-cancer drug, since PPARγ ligands such as ciglitazone (Cig) frequently cause cell death in many types of cancer cells and suppress tumor growth. However, many cancer patients acquire chemo-resistance or radio-resistance after chemo or radiotherapy, and it is still unclear. In the difficulty of well-known anti-cancer drugs, we developed a novel PPARγ agonist CB13 (1-benzyl-5-(4-methylphenyl) pyrido [2,3-d]pyrimidine-2,4(1H,3H)-dione) and investigated the anti-cancer effect and cell death mechanism on human non-small cell lung cancer (NSCLC) cells. With anti-cancer effect of Cig, CB13 also causes inhibition of cell growth by decreasing cell viability, increasing the release of LDH, and increasing caspase-3, and caspase-9 activities. CB13 generates reactive oxygen species (ROS) and causes cell death via ER stress in NSCLC and radio-resistant NSCLC cells (A549R and H460R), and a combination of CB13 and radiation induces greater ER stress and cell death when compared to CB13 alone. Taken together, our results suggest that a combination of CB13 and radiation may overcome radio-resistance caused by radiotherapy.

scholarly journals Neuroprotective Effects of the Anti-cancer Drug Lapatinib Against Epileptic Seizures via Suppressing Glutathione Peroxidase 4-Dependent Ferroptosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Ji-Ning Jia ◽  
Xi-Xi Yin ◽  
Qin Li ◽  
Qi-Wen Guan ◽  
Nan Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Glutathione Peroxidase ◽  
Neuronal Death ◽  
Epileptic Seizures ◽  
Death Process ◽  
Cancer Drug ◽  
Neuroprotective Effects ◽  
Anti Cancer ◽  
Lapatinib Treatment

Epilepsy is a complex neurological disorder characterized by recurrent and unprovoked seizures. Neuronal death process is implicated in the development of repetitive epileptic seizures. Therefore, cell death can be harnessed for ceasing seizures and epileptogenesis. Oxidative stress is regarded as a contributing factor of neuronal death activation and there is compelling evidence supporting antioxidants hold promise in abrogating seizure-related cell modality. Lapatinib, a well-known anti-cancer drug, has been traditionally reported to exert anti-tumor effect via modulating oxidative stress and a recent work illustrates the improvement of encephalomyelitis in rodent models after lapatinib treatment. However, whether lapatinib is beneficial for inhibiting neuronal death and epileptic seizure remains unknown. Here, we found that lapatinib remarkably prevented kainic acid (KA)-epileptic seizures in mice and ferroptosis, a newly defined cell death which is associated with oxidative stress, was involved in the neuroprotection of lapatinib. In the ferroptotic cell death model, lapatinib exerted neuroprotection via restoring glutathione peroxidase 4 (GPX4). Treatment with GPX4 inhibitor ras-selective lethal small molecule 3 (RSL3) abrogated its anti-ferroptotic potential. In a mouse model of KA-triggered seizure, it was also validated that lapatinib blocked GPX4-dependent ferroptosis. It is concluded that lapatinib has neuroprotective potential against epileptic seizures via suppressing GPX4-mediated ferroptosis.

scholarly journals Effects of swainsonine on rat liver and kidney: biochemical and morphological studies.

1985 ◽  
Vol 101 (2) ◽  
pp. 339-349 ◽  
Author(s):  
P M Novikoff ◽  
O Touster ◽  
A B Novikoff ◽  
D P Tulsiani
Keyword(s):  
Cell Death ◽  
Kidney Cells ◽  
Plant Toxin ◽  
Liver Size ◽  
Morphological Studies ◽  
Liver And Kidney ◽  
Ultrastructural Appearance ◽  
Lysosomal System ◽  
Mitotic Figures ◽  
Convoluted Tubules

Among the reported effects of the plant toxin swainsonine in animals are a decreased level of Golgi mannosidase II activity, an increase in lysosomal alpha-D-mannosidase activity, oligosaccharide accumulation, vacuolization of cells, and neurological changes. We now find that, in the rat, the alkaloid rapidly induces vacuolization of both liver and kidney cells, but oligosaccharides accumulate only in the latter. We demonstrate by enzyme- and immunocytochemistry that the induced pleomorphic vacuoles are lysosomal in nature. The vacuoles do not appear to be derived from the Golgi apparatus, which retains its typical ultrastructural appearance, but are formed by autophagy. In swainsonine-fed rats, the lysosomal system is highly developed in hepatocytes, Kupffer cells, and cells of the proximal convoluted tubules. The relation of this hypertrophy of the lysosomal system to the known effects of swainsonine on glycoprotein biosynthesis and on Golgi and lysosomal alpha-mannosidases is not clear. In addition, in liver there occurs a marked increase in mitotic figures in the hepatocytes. This occurred in the absence of both cell death and increased liver size as estimated by gross morphology.

Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II

2011 ◽  
Vol 82 (12) ◽  
pp. 1843-1852 ◽  
Author(s):  
Viviane Brel ◽  
Jean-Philippe Annereau ◽  
Stéphane Vispé ◽  
Anna Kruczynski ◽  
Christian Bailly ◽  
...  
Keyword(s):  
Cell Death ◽  
Topoisomerase Ii ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cell Death Mechanisms

An Aptamer Bio-barCode (ABC) assay using SPR, RNase H, and probes with RNA and gold-nanorods for anti-cancer drug screening

The Analyst ◽  
2017 ◽  
Vol 142 (19) ◽  
pp. 3579-3587 ◽  
Author(s):  
Jacky Fong-Chuen Loo ◽  
Chengbin Yang ◽  
Hing Lun Tsang ◽  
Pui Man Lau ◽  
Ken-Tye Yong ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Gold Nanorods ◽  
Drug Screening ◽  
Rnase H ◽  
Cancer Drug ◽  
Next Generation ◽  
Anti Cancer ◽  
A Cell

We have developed a next generation aptamer-based bio-barcode (ABC) assay to detect cytochrome-c (Cyto-c), a cell death marker released from cancer cells, for anti-cancer drug screening.

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