scholarly journals Effects of alpha, beta momorcharin fruit extract with the combination of Cyclophosphamide in the treatment of glioma cancer In-vivo

2021 ◽  
Vol 2 (1) ◽  
pp. 151-156
Author(s):  
Gunasekar Manoharan ◽  
Bhargava Gottam
Keyword(s):  
Cell Line ◽  
Xenobiotic Metabolism ◽  
Cellular Mechanisms ◽  
African Countries ◽  
Fruit Extract ◽  
The Usa ◽  
The Individual ◽  
And Oxidative Stress ◽  
Scientific Name

The vegetable Momordica charantia L., (family: Cucurbitaceae) is a scientific name of the plant and its fruit. It is also known by other names, for instance in the USA it is known as Bitter gourd or balsam pear while it’s referred to as the African cucumber in many African countries. M. charantia is believed to posse’s anti-carcinogenic properties and it can modulate its effect via xenobiotic metabolism and oxidative stress. This study was specifically designed to investigate the cellular mechanisms whereby α, β momorcharin an extract of M. charantia can induce cell death with the combination of Cyclophosphamide. Different concentration (200µM - 1000µM) of the α, β momorcharin fruit extract were treated (24 hrs incubation) separately with three different cancer cell lines 1321N1, Gos-3, U87-MG and normal L6 muscle cell line. The results also show that Cyclophosphamide (250 µg) with (1000 µM) of the α, β momorcharin extract of M. charantia, and result in significant decreases in cell viability for each cell line, these effects were additive compared to the individual effect of Cyclophosphamide.

scholarly journals Effects of alpha, beta momorcharin fruit extract with the combination of paclitaxel in the treatment of glioma cancer in-vivo.

2019 ◽  
pp. 2-6
Author(s):  
GUNASEKAR MANOHARAN
Keyword(s):  
Cell Line ◽  
Xenobiotic Metabolism ◽  
Cellular Mechanisms ◽  
African Countries ◽  
Fruit Extract ◽  
The Usa ◽  
The Individual ◽  
And Oxidative Stress ◽  
Scientific Name

The vegetable Momordica charantia L., (family: Cucurbitaceae) is a scientific name of the plant and its fruit. It is also known by other names, for instance in the USA it is known as Bitter gourd or balsam pear while its referred to as the African cucumber in many African countries.  M.charantiais believed to posse’s anti-carcinogenic properties and it can modulate its effect via xenobiotic metabolism and oxidative stress. This study was specifically designed to investigate the cellular mechanisms whereby α, β momorcharin an extract of M. charantiacan induce cell death with the combination of paclitaxel.  Different concentration (200µM - 1000µM)of the α, β momorcharin fruit extract were treated (24 hrs incubation) separately with three different cancer cell lines 1321N1, Gos-3, U87-MG and normal L6 muscle cell line. The results also show that paclitaxel(250 µg) with (1000 µM) of the α, β momorcharinextract of M. Charantia,and result in significant decreases in cell viability for each cell line, these effects were additive compared to the individual effect of paclitaxel.    

Structure–function analysis of full-length midkine reveals novel residues important for heparin binding and zebrafish embryogenesis

2013 ◽  
Vol 451 (3) ◽  
pp. 407-415 ◽  
Author(s):  
Jackwee Lim ◽  
Sheng Yao ◽  
Martin Graf ◽  
Christoph Winkler ◽  
Daiwen Yang
Keyword(s):  
Function Analysis ◽  
Structural Features ◽  
Full Length ◽  
Domain Growth ◽  
Heparin Binding ◽  
Cellular Mechanisms ◽  
The Individual ◽  
Zebrafish Embryogenesis

Midkine is a heparin-binding di-domain growth factor, implicated in many biological processes as diverse as angiogenesis, neurogenesis and tumorigenesis. Elevated midkine levels reflect poor prognosis for many carcinomas, yet the molecular and cellular mechanisms orchestrating its activity remain unclear. At the present time, the individual structures of isolated half domains of human midkine are known and its functionally active C-terminal half domain remains a popular therapeutic target. In the present study, we determined the structure of full-length zebrafish midkine and show that it interacts with fondaparinux (a synthetic highly sulfated pentasaccharide) and natural heparin through a previously uncharacterized, but highly conserved, hinge region. Mutating six consecutive residues in the conserved hinge to glycine strongly abates heparin binding and midkine embryogenic activity. In contrast with previous in vitro studies, we found that the isolated C-terminal half domain is not active in vivo in embryos. Instead, we have demonstrated that the N-terminal half domain is needed to enhance heparin binding and mediate midkine embryogenic activity surprisingly in both heparin-dependent and -independent manners. Our findings provide new insights into the structural features of full-length midkine relevant for embryogenesis, and unravel additional therapeutic routes targeting the N-terminal half domain and conserved hinge.

scholarly journals NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis

2010 ◽  
Vol 191 (6) ◽  
pp. 1113-1125 ◽  
Author(s):  
Gang Li ◽  
Christopher Scull ◽  
Lale Ozcan ◽  
Ira Tabas
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Stress Oxidative ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Endoplasmic reticulum (ER)–induced apoptosis and oxidative stress contribute to several chronic disease processes, yet molecular and cellular mechanisms linking ER stress and oxidative stress in the setting of apoptosis are poorly understood and infrequently explored in vivo. In this paper, we focus on a previously elucidated ER stress–apoptosis pathway whose molecular components have been identified and documented to cause apoptosis in vivo. We now show that nicotinamide adenine dinucleotide phosphate reduced oxidase (NOX) and NOX-mediated oxidative stress are induced by this pathway and that apoptosis is blocked by both genetic deletion of the NOX subunit NOX2 and by the antioxidant N-acetylcysteine. Unexpectedly, NOX and oxidative stress further amplify CCAAT/enhancer binding protein homologous protein (CHOP) induction through activation of the double-stranded RNA–dependent protein kinase (PKR). In vivo, NOX2 deficiency protects ER-stressed mice from renal cell CHOP induction and apoptosis and prevents renal dysfunction. These data provide new insight into how ER stress, oxidative stress, and PKR activation can be integrated to induce apoptosis in a pathophysiologically relevant manner.

In Vivo Screening for Tumor Suppressors In Hematological Malignancies Using Barcode RNAi

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 998-998
Author(s):  
Roland Jäger ◽  
Markus Muellner ◽  
Florian Grebien ◽  
Thorsten Klampfl ◽  
Ashot Harutyunyan ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Suppressors ◽  
Hematological Malignancies ◽  
Post Transplantation ◽  
Knock Down ◽  
Bar Codes ◽  
Set Up ◽  
The Individual ◽  
Over Time

Abstract Abstract 998 Chromosomal deletions are frequent cytogenetic defects in hematological malignancies. Common deleted regions (CDRs) defined by the minimal physical overlap of all deletion events are thought to harbor tumor suppressors relevant for pathogenesis. Haploinsufficiency is likely to be a common consequence of chromosomal deletions affecting the function of tumor suppressors within the deleted locus. The use of RNA interference (RNAi) offers a unique opportunity to mimick haploinsufficiency by partial knock-down of the gene transcripts. Since deletions are usually large containing a high number of candidate genes, we aimed to develop a screening method targeting several candidates at once and assaying for tumor suppressor features in a pool of knock-downs. As a model for our approach we selected a CDR on chromosome 20q frequently found clonal in myeloid diseases. We established a screen for knock-downs causing cytokine hypersensitivity. This CDR (physical position chr20:38.7- 42.2) spans 3.5Mb and contains 16 genes (MAFB-JPH2). We cloned 3 short hairpin RNAs (shRNAs) for each mouse homologue of the 16 target genes into the pLKO.2 lentiviral vector. The 48 shRNA constructs were “bar-coded” with different, unique 24bp DNA bar-codes, that can be identified and quantified using the microbead-based xMAP technology (Luminex). We lentivirally delivered the constructs independently into the erythropoietin (Epo) dependent murine cell line Baf3/EpoR, pooled the individual knock-downs in equal amounts and assayed for cytokine hypersensitivity based proliferation advantage under stringent Epo concentrations. Applying a scoring system based on the relative increase/decrease of the individual bar-codes in the pool over time, we could identify the knock-down of topoisomerase 1 (Top1) to induce Epo-concentration dependent outgrowth. Two different Top1 shRNA constructs succeeded in consistently mediating proliferative advantage in three biological replicates. We set up a validation experiment pooling Top1 knock-down cells with control cells (bar-coded, no shRNA) in a 1:1 ratio and could observe significant dominance of the Top1 knock-down cells establishing after 10–15 days in culture and increasing over time (p<0.0001). Knock-down efficiency of both successful constructs measured by qPCR and was consistently between 30–60% of control cell mRNA expression. Based on the convincing cell line data we set up an in vivo validation in a competitive repopulation mouse model. We established a protocol for lentiviral transduction of murine lineage depleted (lin-) bone marrow progenitor cells. Transplanting in a 1:1 ratio of Top1 knock-down and control progenitors into three lethally irradiated mice, we surprisingly observed an outcome opposite to the cell line results. Top1 knock-down progenitors showed a clear disadvantage in repopulation capacity, being underrepresented in the peripheral blood at week 3 post-transplantation and furthermore fully outcompeted by the control cells around week 15 post-transplantation. Based on the unreliability of cell line models in our setup we repeated the screen with the full library (48 shRNAs) in vivo. Two different constructs targeting phospholipase C gamma 1 (Plcg1) had the top score in 3 out of 5 transplanted mice, resulting in an impressive cumulative score. Showing equal representation with the other knock-downs (approximately 2%) in the donor pool, Plcg1 knock-down cells represented up to 13% of the peripheral blood cells at week 3 post- transplant, increasing to up to 29% at week 7 post-transplant. Our results suggest that cell lines often might not be the proper model for studying growth regulation. Further, our in vivo screen revealed Plcg1 as a promising candidate with a tumor suppressor function in hematopoiesis. Disclosures: No relevant conflicts of interest to declare.

Ultrastructural Study of a differentiating human colon carcinoma cell line

1990 ◽  
Vol 48 (3) ◽  
pp. 208-209
Author(s):  
Sylvie Polak-Charcon ◽  
Mehrdad Hekmati ◽  
Yehuda Ben Shaul
Keyword(s):  
Cell Line ◽  
Morphological Changes ◽  
Secretory Granules ◽  
Human Colon ◽  
Cell Types ◽  
Culture Conditions ◽  
Morphological Evidence ◽  
Human Colon Carcinoma Cell ◽  
Colon Cell

The epithelium of normal human colon mucosa “in vivo” exhibits a gradual pattern of differentiation as undifferentiated stem cells from the base of the crypt of “lieberkuhn” rapidly divide, differentiate and migrate toward the free surface. The major differentiated cell type of the intestine observed are: absorptive cells displaying brush border, goblet cells containing mucous granules, Paneth and endocrine cells containing dense secretory granules. These different cell types are also found in the intestine of the 13-14 week old embryo.We present here morphological evidence showing that HT29, an adenocarcinoma of the human colon cell line, can differentiate into various cell types by changing the growth and culture conditions and mimic morphological changes found during development of the intestine in the human embryo.HT29 cells grown in tissue-culture dishes in DMEM and 10% FCS form at late confluence a multilayer of morphologically undifferentiated cell culture covered with irregular microvilli, and devoid of tight junctions (Figs 1-3).

Cytotoxicity of chitosan ultrafine nanoshuttles on MCF-7 cell line as surrogate model for breast cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Tarek Faris ◽  
Gamaleldin I. Harisa ◽  
Fars K. Alanazi ◽  
Mohamed M. Badran ◽  
Afraa Mohammad Alotaibi ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Factorial Design ◽  
Cell Line ◽  
Cell Lines ◽  
Blood Cells ◽  
Sodium Tripolyphosphate ◽  
Physicochemical Characterization ◽  
Spherical Shape ◽  
Mcf 7

Aim: This study aimed to explore an affordable technique for the fabrication of Chitosan Nanoshuttles (CSNS) at the ultrafine nanoscale less than 100 nm with improved physicochemical properties, and cytotoxicity on the MCF-7 cell line. Background: Despite several studies reported that the antitumor effect of CS and CSNS could achieve intracellular compartment target ability, no enough available about this issue and further studies are required to address this assumption. Objectives: The objective of the current study was to investigate the potential processing variables for the production of ultrafine CSNS (> 100 nm) using Box-Benhken Design factorial design (BBD). This was achieved through a study of the effects of processing factors, such as CS concentration, CS/TPP ratio, and pH of the CS solution, on PS, PDI, and ZP. Moreover, the obtained CSNS was evaluated for physicochemical characteristics, morphology Also, hemocompatibility, and cytotoxicity using Red Blood Cells (RBCs) and MCF-7 cell lines were investigated. Methods: Box-Benhken Design factorial design (BBD) was used in the analysis of different selected variables. The effects of CS concentration, sodium tripolyphosphate (TPP) ratio, and pH on particle size, Polydispersity Index (PDI), and Zeta Potential (ZP) were measured. Subsequently, the prepared CS nanoshuttles were exposed to stability studies, physicochemical characterization, hemocompatibility, and cytotoxicity using red blood cells and MCF-7 cell lines as surrogate models for in vivo study. Result: The present results revealed that the optimized CSNS have ultrafine nanosize, (78.3±0.22 nm), homogenous with PDI (0.131±0.11), and ZP (31.9±0.25 mV). Moreover, CSNS have a spherical shape, amorphous in structure, and physically stable. Also, CSNS has biological safety as indicated by a gentle effect on red blood cell hemolysis, besides, the obtained nanoshuttles decrease MCF-7 viability. Conclusion: The present findings concluded that the developed ultrafine CSNS has unique properties with enhanced cytotoxicity. thus promising for use in intracellular organelles drug delivery.

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