scholarly journals Antiproliferative Activity of the Isofuranonaphthoquinone Isolated fromBulbine frutescensagainst Jurkat T Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Penelope Tambama ◽  
Berhanu Abegaz ◽  
Stanley Mukanganyama
Keyword(s):  
T Cells ◽  
Anticancer Drug ◽  
Glutathione Transferase ◽  
Reduced Glutathione ◽  
Synergistic Effects ◽  
Drug Efflux ◽  
Cellular Mechanisms ◽  
Jurkat T Cells ◽  
Public Health Burden ◽  
Drug Efflux Pumps

Cancer is a major public health burden in both developed and developing countries. The quinone moiety has been shown to possess antitumor activity and several cancer drugs in clinical use contain this entity. The effect of isofuranonaphthoquinone isolated fromBulbine frutescenson Jurkat T cells was determined. Cells were exposed to the isofuranonaphthoquinone (IFNQ) at different concentrations. Significant antiproliferative effects were observed which were comparable to that of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A combination of IFNQ with BCNU produced synergistic effects which were observed after 72 hrs. It was also observed that combining IFNQ with reduced glutathione abolished the anticancer activity of the compound. It is, therefore, proposed that the isofuranonaphthoquinone may exert part of its effect by producing reactive oxygen species resulting in death of the cells as the effects of this compound were antagonized by reduced glutathione. An investigation on the effects of isofuranonaphthoquinone on glutathione transferase (GST) activity and drug efflux pumps showed that this compound exhibited inhibitory effects on both the GST and the drug efflux pumping activities. Thus, the isofuranonaphthoquinone showed cytotoxicity, works through inhibition of some cellular mechanisms, and could present a potential source of lead compounds for anticancer drug development.

scholarly journals Constituents of French Marigold (Tagetes patulaL.) Flowers Protect Jurkat T-Cells against Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Irakli Chkhikvishvili ◽  
Tamar Sanikidze ◽  
Nunu Gogia ◽  
Maia Enukidze ◽  
Marine Machavariani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
T Cells ◽  
Radical Scavenging ◽  
Jurkat Cells ◽  
Cellular Mechanisms ◽  
Jurkat T Cells ◽  
Radical Scavenging Capacity ◽  
Scavenging Capacity ◽  
Anti Inflammatory

The flowers of French marigold (Tagetes patulaL.) are widely used in folk medicine, in particular for treating inflammation-related disorders. However, cellular mechanisms of this activity demand further investigation. In the present work, we studied the potential ofT. patulacompounds to alleviate the oxidative stress in hydrogen peroxide-challenged human lymphoblastoid Jurkat T-cells. Crude extracts of marigold flowers and purified fractions containing flavonoids patuletin, quercetagetin, and quercetin and their derivatives, as well as the carotenoid lutein, were brought in contact with Jurkat cells challenged with 25 or 50 μM H2O2. Hydrogen peroxide caused oxidative stress in the cells, manifested as generation of superoxide and peroxyl radicals, reduced viability, arrested cell cycle, and enhanced apoptosis. The stress was alleviated by marigold ingredients that demonstrated high radical-scavenging capacity and enhanced the activity of antioxidant enzymes involved in neutralization of reactive oxygen species. Flavonoid fraction rich in quercetin and quercetagetin showed the highest cytoprotective activity, while patuletin in high dose exerted a cytotoxic effect associated with its anticancer potential.T. patulacompounds enhanced the production of anti-inflammatory and antioxidant interleukin-10 (IL-10) in Jurkat cells. Both direct radical-scavenging capacity and stimulation of protective cellular mechanisms can underlay the anti-inflammatory properties of marigold flowers.

scholarly journals Rosmarinic Acid-Rich Extracts of Summer Savory (Satureja hortensisL.) Protect Jurkat T Cells against Oxidative Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Irakli Chkhikvishvili ◽  
Tamar Sanikidze ◽  
Nunu Gogia ◽  
Tamar Mchedlishvili ◽  
Maia Enukidze ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Rosmarinic Acid ◽  
Jurkat Cells ◽  
Peroxyl Radicals ◽  
G1 Arrest ◽  
Acid Fraction ◽  
Cellular Mechanisms ◽  
Jurkat T Cells ◽  
Phenolic Fraction

Summer savory (Satureja hortensisL.,Lamiaceae) is used in several regions of the world as a spice and folk medicine. Anti-inflammatory and cytoprotective effects ofS. hortensisand of its rosmarinic acid-rich phenolic fraction have been demonstrated in animal trials. However, previous studies of rosmarinic acid in cell models have yielded controversial results. In this study, we investigated the effects of summer savory extracts on H2O2-challenged human lymphoblastoid Jurkat T cells. LC-MS analysis confirmed the presence of rosmarinic acid and flavonoids such as hesperidin and naringin in the phenolic fraction. Adding 25 or 50 µM of H2O2to the cell culture caused oxidative stress, manifested as generation of superoxide and peroxyl radicals, reduced cell viability, G0/G1 arrest, and enhanced apoptosis. This stress was significantly alleviated by the ethanolic and aqueous extracts ofS. hortensisand by the partially purified rosmarinic acid fraction. The application of an aqueousS. hortensisextract doubled the activity of catalase and superoxide dismutase in the cells. The production of IL-2 and IL-10 interleukins was stimulated by H2O2and was further enhanced by the addition of theS. hortensisextract or rosmarinic acid fraction. The H2O2-challenged Jurkat cells may serve as a model for investigating cellular mechanisms of cytoprotective phytonutrient effects.

The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells

2009 ◽  
pp. 1-8
Author(s):  
Jing-Lei Qu ◽  
Xiu-Juan Qu ◽  
Ming-Fang Zhao ◽  
Yue-E Teng ◽  
Ye Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Ubiquitin Ligases ◽  
Jurkat T Cells ◽  
Induced Apoptosis

Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems

2018 ◽  
Vol 25 (28) ◽  
pp. 3319-3332 ◽  
Author(s):  
Chuanmin Zhang ◽  
Shubiao Zhang ◽  
Defu Zhi ◽  
Jingnan Cui
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Resistance Mechanisms ◽  
Delivery Systems ◽  
Cell Cycle Checkpoints ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
Cancer Models ◽  
Anti Cancer

There are several mechanisms by which cancer cells develop resistance to treatments, including increasing anti-apoptosis, increasing drug efflux, inducing angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs are hard to reach curative effects due to these resistance mechanisms. It has been suggested that liposomes based co-delivery systems, which can deliver drugs and genes to the same tumor cells and exhibit synergistic anti-cancer effects, could be used to overcome the resistance of cancer cells. As the co-delivery systems could simultaneously block two or more pathways, this might promote the death of cancer cells by sensitizing cells to death stimuli. This article provides a brief review on the liposomes based co-delivery systems to overcome cancer resistance by the synergistic effects of drugs and genes. Particularly, the synergistic effects of combinatorial anticancer drugs and genes in various cancer models employing multifunctional liposomes based co-delivery systems have been discussed. This review also gives new insights into the challenges of liposomes based co-delivery systems in the field of cancer therapy, by which we hope to provide some suggestions on the development of liposomes based co-delivery systems.

The Role of NIR Fluorescence in MDR Cancer Treatment: From Targeted Imaging to Phototherapy

2020 ◽  
Vol 27 (33) ◽  
pp. 5510-5529
Author(s):  
Zengtao Wang ◽  
Qingqing Meng ◽  
Shaoshun Li
Keyword(s):  
Cancer Treatment ◽  
Near Infrared ◽  
Combined Therapy ◽  
Efflux Pumps ◽  
Cross Resistance ◽  
Great Promise ◽  
Drug Efflux ◽  
Nir Dyes ◽  
Nir Imaging ◽  
Drug Efflux Pumps

Background: Multidrug Resistance (MDR) is defined as a cross-resistance of cancer cells to various chemotherapeutics and has been demonstrated to correlate with drug efflux pumps. Visualization of drug efflux pumps is useful to pre-select patients who may be insensitive to chemotherapy, thus preventing patients from unnecessary treatment. Near-Infrared (NIR) imaging is an attractive approach to monitoring MDR due to its low tissue autofluorescence and deep tissue penetration. Molecular NIR imaging of MDR cancers requires stable probes targeting biomarkers with high specificity and affinity. Objective: This article aims to provide a concise review of novel NIR probes and their applications in MDR cancer treatment. Results: Recently, extensive research has been performed to develop novel NIR probes and several strategies display great promise. These strategies include chemical conjugation between NIR dyes and ligands targeting MDR-associated biomarkers, native NIR dyes with inherent targeting ability, activatable NIR probes as well as NIR dyes loaded nanoparticles. Moreover, NIR probes have been widely employed for photothermal and photodynamic therapy in cancer treatment, which combine with other modalities to overcome MDR. With the rapid advancing of nanotechnology, various nanoparticles are incorporated with NIR dyes to provide multifunctional platforms for controlled drug delivery and combined therapy to combat MDR. The construction of these probes for MDR cancers targeted NIR imaging and phototherapy will be discussed. Multimodal nanoscale platform which integrates MDR monitoring and combined therapy will also be encompassed. Conclusion: We believe these NIR probes project a promising approach for diagnosis and therapy of MDR cancers, thus holding great potential to reach clinical settings in cancer treatment.

Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines

2020 ◽  
Vol 20 (8) ◽  
pp. 1017-1027
Author(s):  
Abdul M. Baig ◽  
Zohaib Rana ◽  
Mohammad M. Mannan ◽  
Areeba Khaleeq ◽  
Fizza Nazim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Drug Efflux ◽  
Adapter Proteins ◽  
Cancer Drugs ◽  
Protein Targets ◽  
Anti Cancer ◽  
Drug Efflux Pumps ◽  
Cancer Agent ◽  
Androgen Independent

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs. Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa). Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines. Results: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects. Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.

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