EXPERIMENTAL STUDIES (IN VITRO) ON THE BIOLOGICAL EFFECTS OF CERTAIN LUNG CELL & CELL LINES AFTER ALPHA IRRADIATION OF 238Pu

To understand the cause of the biological effects of xenobiotic metabolism in mammals, investigators have traditionally performed animal experiments by comparing the results of biochemical methods, such as measurement of enzyme activity analysis of the metabolites produced, with the observed toxicological effect. This article deals with in vitro methods for genotoxicity combined with drug metabolising preparations at the organelle, cell or organ levels, as exemplified by microsome preparations, isolated cells/cell lines and organ perfusion systems, respectively. The advantage of some of these methods for studying metabolism-mediated mutagenicity is that the measured endpoint reflects not only the bioactivating phase I reactions, but also the detoxifying phase II reactions, and the transfer of the non-conjugated reactive metabolites to other cells and their ability to cause mutations in these cells. In vivo, all these events are important factors in the initiation of cancer. A mechanistic advantage of the methods for metabolism-mediated mutagenicity in vitro is that the relevance of the different steps in metabolism for the mutational events can seldom be investigated in an in vivo assay. Furthermore, human studies can easily be performed using the co-culture technique with isolated human cells or cell lines.

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Biological effects of ultrasound exposure on adriamycin-resistant and cisplatin-resistant human ovarian carcinoma cell lines in vitro

Ultrasonics Sonochemistry ◽

10.1016/s1350-4177(03)00160-3 ◽

2004 ◽

Vol 11 (2) ◽

pp. 89-94 ◽

Cited By ~ 15

Author(s):

Tinghe Yu ◽

Jin Bai ◽

Kai Hu ◽

Zhibiao Wang

Keyword(s):

Ovarian Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Biological Effects ◽

Ultrasound Exposure ◽

Human Ovarian Carcinoma Cell ◽

Carcinoma Cell Lines ◽

Human Ovarian Carcinoma

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SyNPL: Synthetic Notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

10.1101/2021.09.24.461672 ◽

2021 ◽

Author(s):

Mattias Malaguti ◽

Rosa Portero Migueles ◽

Jennifer Annoh ◽

Daina Sadurska ◽

Guillaume Blin ◽

...

Keyword(s):

Cell Fate ◽

Cell Lines ◽

Modular Design ◽

Cell Interactions ◽

Cell Populations ◽

Cell Contact ◽

Pluripotent Cells ◽

Cell Fate Decisions ◽

Cell Cell

ABSTRACTCell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack of efficient analysis tools. Here we introduce SyNPL: clonal pluripotent stem cell lines which employ optimised Synthetic Notch (SynNotch) technology to report cell-cell interactions between engineered “sender” and “receiver” cells in cultured pluripotent cells and chimaeric mouse embryos. A modular design makes it straightforward to adapt the system for programming differentiation decisions non-cell-autonomously in receiver cells in response to direct contact with sender cells. We demonstrate the utility of this system by enforcing neuronal differentiation at the boundary between two cell populations. In summary, we provide a new tool which could be used to identify cell interactions and to profile changes in gene or protein expression that result from direct cell-cell contact with defined cell populations in culture and in early embryos, and which can be adapted to generate synthetic patterning of cell fate decisions.

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JS-K, a GST-Activated Nitric Oxide Generator, Induces Apoptosis and Overcomes In Vitro Drug Resistance in Multiple Myeloma Cells.

Blood ◽

10.1182/blood.v106.11.1593.1593 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1593-1593

Author(s):

Tanyel Kiziltepe ◽

Kenji Ishitsuka ◽

Teru Hideshima ◽

Noopur Raje ◽

Norihiko Shiraishi ◽

...

Keyword(s):

Nitric Oxide ◽

Multiple Myeloma ◽

Drug Resistance ◽

Tumor Cells ◽

Cell Lines ◽

Biological Effects ◽

Treatment Modalities ◽

Cancer Drug ◽

Induced Apoptosis

Abstract Multiple myeloma (MM) is currently an incurable hematological malignancy. A major reason for the failure of currently existing therapies is the chemotherapeutic resistance acquired by the MM cells upon treatment. Overexpression of glutathione S-transferases (GST) has been shown as one possible mechanism of anti-cancer drug resistance in a broad spectrum of tumor cells. JS-K (O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate) belongs to a class of pro-drugs which are designed to release nitric oxide (NO) on reaction with GST. JS-K can possibly turn GST overexpression to the tumor’s disadvantage by (1) consuming intracellular GSH and preventing drug inactivation; and (2) by exposing tumor cells to high intracellular concentrations of NO. JS-K has potent in vitro and in vivo anti-leukemic activity. The purpose of the present study is to examine the biological effects of JS-K on human MM cells. We demonstrate that JS-K has significant in vitro cytotoxicity on MM cell lines, with an IC50 of 0.3-2 mM at 48 hours. JS-K also induces cytotoxicity on cell lines that are resistant to conventional chemotherapy (i.e., MM1R, RPMI-Dox40, RPMI-LR5, RPMI-MR20). Importantly, no cytotoxic effects of JS-K were detected on peripheral blood mononuclear cells (PBMNC) obtained from healthy volunteers at these doses. Moreover, JS-K could overcome the survival and growth advantages conferred by interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells (BMSC). JS-K caused a transient G2/M arrest followed by apoptosis, as determined by flow cytometric analysis using PI, Annexin V and Apo2.7 staining. JS-K-induced apoptosis was associated with caspase 8, 7, 9 and 3 activation. Interestingly, Fas was upregulated by JS-K, suggesting the involvement of death receptor pathway in induction of apoptosis. JS-K also triggered Mcl-1 cleavage and Bcl-2 phosphorylation, suggesting the involvement of mitochondrial pathway. In addition, apoptosis inducing factor (AIF), endonuclease G (EndoG) and cytochrome c were released into the cytosol during apoptosis. Taken together, these findings suggest the involvement of both intrinsic and extrinsic apoptotic pathways in JS-K-induced apoptosis in MM cells. In summary, our studies demonstrate that JS-K induces apoptosis and overcomes in vitro drug resistance in MM cells. Therefore, JS-K is a novel compound which carries significant potential to be included in the repertoire of existing treatment modalities for MM. Ongoing studies are delineating the mechanism of action of JS-K to provide the preclinical rationale for combination therapies to overcome drug resistance and improve patient outcome.

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Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nel003 ◽

2006 ◽

Vol 3 (2) ◽

pp. 237-247 ◽

Cited By ~ 48

Author(s):

Mepur H. Ravindranath ◽

Thiruverkadu S. Saravanan ◽

Clarence C. Monteclaro ◽

Naftali Presser ◽

Xing Ye ◽

...

Keyword(s):

Prostate Cancer ◽

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cell Lines ◽

Green Tea ◽

Cancer Cell ◽

Human Cancer ◽

Biological Effects ◽

Cancer Cell Lines

The anticancer potential of catechins derived from green tea is not well understood, in part because catechin-related growth suppression and/or apoptosis appears to vary with the type and stage of malignancy as well as with the type of catechin. Thisin vitrostudy examined the biological effects of epicatechin (EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate (EGCG) in cell lines from human gender-specific cancers. Cell lines developed from organ-confined (HH870) and metastatic (DU145) prostate cancer, and from moderately (HH450) and poorly differentiated (HH639) epithelial ovarian cancer were grown with or without EC, EGC, ECG or EGCG. When untreated cells reached confluency, viability and doubling time were measured for treated and untreated cells. Whereas EC treatment reduced proliferation of HH639 cells by 50%, EGCG suppressed proliferation of all cell lines by 50%. ECG was even more potent: it inhibited DU145, HH870, HH450 and HH639 cells at concentrations of 24, 27, 29 and 30 µM, whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells at concentrations 89, 45, 62 and 42 µM. When compared with EGCG, ECG more effectively suppresses the growth of prostate cancer and epithelial ovarian cancer cell lines derived from tumors of patients with different stages of disease.

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Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle

Journal of Chemistry ◽

10.1155/2013/191563 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

A. Byczek ◽

J. Zawisza-Puchalka ◽

A. Gruca ◽

K. Papaj ◽

G. Grynkiewicz ◽

...

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Biological Effects ◽

Cancer Cell Lines ◽

Dna Lesions ◽

Hydroxyl Group ◽

Human Cancer Cell Lines

Our previous studies on antiproliferative properties of genistein derivatives substituted at C7 hydroxyl group of the ring A revealed some compounds with antimitotic properties. The aim of this work was to synthesize their analogues substituted at the 4′-position of the ring B in genistein and to define their antiproliferative mechanism of action in selected cancer cell linesin vitro. C4′-substituted glycoconjugates were obtained in a three-step procedure: (1) alkylation with anω-bromoester; (2) deacylation; (3) Ferrier-type rearrangement glycosylation with acylated glycals. Biological effects including antiproliferative effects of the compounds, cell cycle, DNA lesions (ATM activation, H2A.X phosphorylation, and micronuclei formation), and autophagy were studied in human cancer cell lines. Some of the tested derivatives potently inhibited cell proliferation. The presence of a substituent at the 4′-position of the ring B in genistein correlated to a p53-independent G1 cell-cycle arrest. The derivatives substituted at C4′ did not induce DNA lesions and appeared to be nongenotoxic. The tested compounds induced autophagy and caused remarkable decrease of cell volume.

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The E3 Ubiquitin Ligase NEDD4-1 Mediates Temozolomide-Resistant Glioblastoma through PTEN Attenuation and Redox Imbalance in Nrf2–HO-1 Axis

International Journal of Molecular Sciences ◽

10.3390/ijms221910247 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10247

Author(s):

Hao-Yu Chuang ◽

Li-Yun Hsu ◽

Chih-Ming Pan ◽

Narpati Wesa Pikatan ◽

Vijesh Kumar Yadav ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Lines ◽

Biological Effects ◽

Critical Role ◽

Clinical Samples ◽

Redox Imbalance ◽

Signaling Axis ◽

Resistant Cells

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to chemotherapy, and tumor recurrence is common. Neuronal precursor cell-expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ligase that controls embryonic development and animal growth. NEDD4-1 regulates the tumor suppressor phosphatase and tensin homolog (PTEN), one of the major regulators of the PI3K/AKT/mTOR signaling axis, as well as the response to oxidative stress. Methods: The expression levels of NEDD4-1 in GBM tissues and different cell lines were determined by quantitative real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo assays were performed to explore the biological effects of NEDD4-1 on GBM cells. Temozolomide (TMZ)-resistant U87MG and U251 cell lines were specifically established to determine NEDD4-1 upregulation and its effects on the tumorigenicity of GBM cells. Subsequently, miRNA expression in TMZ-resistant cell lines was investigated to determine the dysregulated miRNA underlying the overexpression of NEDD4-1. Indole-3-carbinol (I3C) was used to inhibit NEDD4-1 activity, and its effect on chemoresistance to TMZ was verified. Results: NEDD4-1 was significantly overexpressed in the GBM and TMZ-resistant cells and clinical samples. NEDD4-1 was demonstrated to be a key oncoprotein associated with TMZ resistance, inducing oncogenicity and tumorigenesis of TMZ-resistant GBM cells compared with TMZ-responsive cells. Mechanistically, TMZ-resistant cells exhibited dysregulated expression of miR-3129-5p and miR-199b-3p, resulting in the induced NEDD4-1 mRNA-expression level. The upregulation of NEDD4-1 attenuated PTEN expression and promoted the AKT/NRF2/HO-1 oxidative stress signaling axis, which in turn conferred amplified defense against reactive oxygen species (ROS) and eventually higher resistance against TMZ treatment. The combination treatment of I3C, a known inhibitor of NEDD4-1, with TMZ resulted in a synergistic effect and re-sensitized TMZ-resistant tumor cells both in vitro and in vivo. Conclusions: These findings demonstrate the critical role of NEDD4-1 in regulating the redox imbalance in TMZ-resistant GBM cells via the degradation of PTEN and the upregulation of the AKT/NRF2/HO-1 signaling pathway. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.

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Integrated Bioinformatics Data Analysis and Experimental Studies Reveals Prognostic Significance of ALDH Family in Endometria Cancer

10.21203/rs.3.rs-427053/v1 ◽

2021 ◽

Author(s):

Zhou-Tong Dai ◽

Yuan Xiang ◽

Xing-Hua Liao

Keyword(s):

Cell Lines ◽

Cox Regression ◽

Prognostic Significance ◽

Experimental Studies ◽

Female Reproductive Tract ◽

The Body ◽

Mouse Tumor ◽

The Impact

Abstract Background Uterine Corpus Endometrial Cancer (UCEC) is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. Methods We used the gene profile data of 33 cancers in the TCGA database to analyze the expression and survival of the ALDH family. GO, KEGG, PPI multiple functional analysis was used to predict the regulatory role of ALDH family in cancer. In addition, using CCK-8, colony formation, nude mouse tumor formation and other methods, the in vitro function of UCEC cancer cell lines was tested to further confirm the key role of ALDH2 expression in the proliferation of UCEC cell lines. Finally, Lasso and Cox regression methods were used to establish an overall survival prognosis model based on ALDH2 expression. Result In our research, we explored the expression of ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. Conclusion This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

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Negative impact of DEP exposure on human airway epithelial cell adhesion, stiffness, and repair

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00039.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. L119-L132 ◽

Cited By ~ 15

Author(s):

Blandine Doornaert ◽

Valerie Leblond ◽

Stephane Galiacy ◽

Gabriel Gras ◽

Emmanuelle Planus ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Inflammatory Cytokines ◽

Negative Impact ◽

Experimental Studies ◽

Diesel Exhaust Particles ◽

Matrix Remodeling ◽

Cell Matrix ◽

Cell Cell

Epidemiological and experimental studies suggest that diesel exhaust particles (DEPs) may be associated with increased respiratory mortality and morbidity. Several recent studies have also shown that DEPs increase the production of inflammatory cytokines by human bronchial epithelium (HBE) cells in vitro. The present study investigates the effects of DEPs on the interaction of l-HBE cells (16HBE14o-) with the cell and matrix microenvironment based on evaluation of integrin-type cell/matrix ligand expression, cytoskeleton (CSK) stiffness, and matrix remodeling via matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression. The results showed that DEP exposure induced: 1) a net dose-dependent decrease in CSK stiffness through actin fibers, 2) a concomitant specific reduction of both α3- and β1-integrin subunits extensively expressed on the HBE cell surface, 3) a decrease in the level of CD44, which is a major HBE cell-cell and HBE cell-matrix adhesion molecule; and 4) an isolated decrease in MMP-1 expression without any change in tissue inhibitor of matrix metalloproteinase (TIMP)-1 or TIMP-2 tissue inhibitors. Restrictive modulation of cell-matrix interaction, cell-cell connection, CSK stiffness, and fibrillary collagen remodeling results in a decreased wound closure capacity and an increased deadhesion capacity. In conclusion, on the basis of these results, we can propose that, in addition to their ability to increase the production of inflammatory cytokines, DEPs could also alter the links between actin CSK and the extracellular matrix, suggesting that they might facilitate HBE cell detachment in vivo.

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