scholarly journals Double-Coated Poly(butyl Cyanoacrylate) Nanoparticles as a Potential Carrier for Overcoming P-Gp- and BCRP-Mediated Multidrug Resistance in Cancer Cells

2021 ◽  
Vol 3 ◽  
Author(s):  
Neeraj Kaushal ◽  
Zhe-Sheng Chen ◽  
Senshang Lin
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Tween 80 ◽  
Cell Uptake ◽  
Glycoprotein P ◽  
Free Doxorubicin ◽  
Overexpressing Cell ◽  
Polymerization Method

The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. Doxorubicin-loaded PBCA-NPs were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 at varied concentrations. MDR reversing potential was investigated by cellular uptake in P-gp overexpressing cell line. And, the outcomes were verified by modified MTT assay in P-gp or BCRP overexpressing cell lines. The findings from the cell uptake study indicate that double-coated PBCA-NPs significantly enhanced doxorubicin accumulation within the cells. MTT assays revealed that double-coated PBCA-NPs significantly potentiated the sensitivity of doxorubicin in P-gp overexpressing cells, in comparison to free doxorubicin, single-, and un-coated PBCA-NPs, respectively. Moreover, further increase in concentration with Tween 80, double-coated PBCA-NPs significantly enhanced the sensitivity of doxorubicin in BCRP overexpressing cell line, in comparison to single- and double-coated formulations (with lower concentration of Tween 80). Hence, it could be concluded that double-coated PBCA-NPs can be used as a potential carrier for enhancing doxorubicin accumulation in MDR cancer cells.

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

2020 ◽  
Vol 20 (23) ◽  
pp. 2070-2079
Author(s):  
Srimadhavi Ravi ◽  
Sugata Barui ◽  
Sivapriya Kirubakaran ◽  
Parul Duhan ◽  
Kaushik Bhowmik
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Atm Kinase ◽  
Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

scholarly journals Retraction Note: Flavonoids modulate multidrug resistance through wnt signaling in P-glycoprotein overexpressing cell lines

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
S. Mohana ◽  
M. Ganesan ◽  
N. Rajendra Prasad ◽  
D. Ananthakrishnan ◽  
D. Velmurugan
Keyword(s):  
Multidrug Resistance ◽  
Wnt Signaling ◽  
Cell Lines ◽  
P Glycoprotein ◽  
Overexpressing Cell

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals In Vitro Spectroscopy-Based Profiling of Urothelial Carcinoma: A Fourier Transform Infrared and Raman Imaging Study

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Monika Kujdowicz ◽  
Wojciech Placha ◽  
Brygida Mech ◽  
Karolina Chrabaszcz ◽  
Krzysztof Okoń ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Fourier Transform ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Malignant Neoplasm ◽  
Fourier Transform Infrared ◽  
Diagnostic Tools ◽  
Label Free ◽  
Bladder Cancer Cells

Markers of bladder cancer cells remain elusive, which is a major cause of the low recognition of this malignant neoplasm and its recurrence. This implies an urgent need for additional diagnostic tools which are based on the identification of the chemism of bladder cancer. In this study, we employed label-free techniques of molecular imaging—Fourier Transform Infrared and Raman spectroscopic imaging—to investigate bladder cancer cell lines of various invasiveness (T24a, T24p, HT-1376, and J82). The urothelial HCV-29 cell line was the healthy control. Specific biomolecules discriminated spatial distribution of the nucleus and cytoplasm and indicated the presence of lipid bodies and graininess in some cell lines. The most prominent discriminators are the total content of lipids and sugar moieties as well as the presence of glycogen and other carbohydrates, un/saturated lipids, cytochromes, and a level of S-S bridges in proteins. The combination of the obtained hyperspectral database and chemometric methods showed a clear differentiation of each cell line at the level of the nuclei and cytoplasm and pointed out spectral signals which differentiated bladder cancer cells. Registered spectral markers correlated with biochemical composition changes can be associated with pathogenesis and potentially used for the diagnosis of bladder cancer and response to experimental therapies.

scholarly journals Encapsulation of Nedaplatin in Novel PEGylated Liposomes Increases Its Cytotoxicity and Genotoxicity against A549 and U2OS Human Cancer Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 863 ◽  
Author(s):  
Salma El-Shafie ◽  
Sherif Ashraf Fahmy ◽  
Laila Ziko ◽  
Nada Elzahed ◽  
Tamer Shoeib ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Following the discovery of cisplatin over 50 years ago, platinum-based drugs have been a widely used and effective form of cancer therapy, primarily causing cell death by inducing DNA damage and triggering apoptosis. However, the dose-limiting toxicity of these drugs has led to the development of second and third generation platinum-based drugs that maintain the cytotoxicity of cisplatin but have a more acceptable side-effect profile. In addition to the creation of new analogs, tumor delivery systems such as liposome encapsulated platinum drugs have been developed and are currently in clinical trials. In this study, we have created the first PEGylated liposomal form of nedaplatin using thin film hydration. Nedaplatin, the main focus of this study, has been exclusively used in Japan for the treatment of non-small cell lung cancer, head and neck, esophageal, bladder, ovarian and cervical cancer. Here, we investigate the cytotoxic and genotoxic effects of free and liposomal nedaplatin on the human non-small cell lung cancer cell line A549 and human osteosarcoma cell line U2OS. We use a variety of assays including ICP MS and the highly sensitive histone H2AX assay to assess drug internalization and to quantify DNA damage induction. Strikingly, we show that by encapsulating nedaplatin in PEGylated liposomes, the platinum uptake cytotoxicity and genotoxicity of nedaplatin was significantly enhanced in both cancer cell lines. Moreover, the enhanced platinum uptake as well as the cytotoxic/antiproliferative effect of liposomal nedaplatin appears to be selective to cancer cells as it was not observed on two noncancer cell lines. This is the first study to develop PEGylated liposomal nedaplatin and to demonstrate the superior cell delivery potential of this product.

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway

2020 ◽  
Vol 52 (11) ◽  
pp. 1202-1214
Author(s):  
Lejia Qiu ◽  
Zhaoxia Ma ◽  
Xiaoran Li ◽  
Yizhang Deng ◽  
Guangling Duan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Nrf2 Pathway ◽  
P Glycoprotein ◽  
New Findings ◽  
Nrf2 Signaling Pathway ◽  
Common Malignancy

Abstract Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

scholarly journals The Effect of Compound Sophora on Fluorouracil and Oxaliplatin Resistance in Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
WeiHua Yin ◽  
GuPing Zhong ◽  
HuiZhen Fan ◽  
HongMei Xia
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Sw480 Cell ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Chemotherapy Drugs ◽  
Protein Levels ◽  
Enhanced Expression

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P<0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P<0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

scholarly journals Flavonoids modulate multidrug resistance through wnt signaling in P-glycoprotein overexpressing cell lines

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
S. Mohana ◽  
M. Ganesan ◽  
N. Rajendra Prasad ◽  
D. Ananthakrishnan ◽  
D. Velmurugan
Keyword(s):  
Multidrug Resistance ◽  
Wnt Signaling ◽  
Cell Lines ◽  
P Glycoprotein ◽  
Overexpressing Cell

scholarly journals Bioelectrical Analysis of Various Cancer Cell Types Immobilized in 3D Matrix and Cultured in 3D-Printed Well

Biosensors ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 136 ◽  
Author(s):  
Paivana ◽  
Mavrikou ◽  
Kaltsas ◽  
Kintzios
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Population ◽  
Cancer Cell Line ◽  
Immobilized Cell ◽  
Impedance Measurements ◽  
Hydrogel Matrix

Cancer cell lines are important tools for anticancer drug research and assessment. Impedance measurements can provide valuable information about cell viability in real time. This work presents the proof-of-concept development of a bioelectrical, impedance-based analysis technique applied to four adherent mammalian cancer cells lines immobilized in a three-dimensional (3D) calcium alginate hydrogel matrix, thus mimicking in vivo tissue conditions. Cells were treated with cytostatic agent5-fluoruracil (5-FU). The cell lines used in this study were SK-N-SH, HEK293, HeLa, and MCF-7. For each cell culture, three cell population densities were chosen (50,000, 100,000, and 200,000 cells/100 μL). The aim of this study was the extraction of mean impedance values at various frequencies for the assessment of the different behavior of various cancer cells when 5-FU was applied. For comparison purposes, impedance measurements were implemented on untreated immobilized cell lines. The results demonstrated not only the dependence of each cell line impedance value on the frequency, but also the relation of the impedance level to the cell population density for every individual cell line. By establishing a cell line-specific bioelectrical behavior, it is possible to obtain a unique fingerprint for each cancer cell line reaction to a selected anticancer agent.

Ganoderic Acid Restores the Sensitivity of Multidrug Resistance Cancer Cells to Doxorubicin

2013 ◽  
Vol 834-836 ◽  
pp. 573-576
Author(s):  
Jing Jing Ouyang ◽  
Yu Qiang Wang ◽  
Wen Tang
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Drug Accumulation ◽  
Ganoderic Acid ◽  
Inhibition Effect ◽  
Induction Of Apoptosis

Ganoderic acid R (GA-R) possessed significant cytotoxicity on a multidrug resistance (MDR) tumor cell line (KB-A-1/Dox) and a sensitive tumor cell line (KB-A-1). The results indicated that the inhibition effect of the GA-R was due to the induction of apoptosis. The use of GA-R in vitro resulted in a restoration response of the KB-A-1/Dox cells to the anti-tumor drug doxorubicin by stimulating the drug accumulation within the cells. The index of MDR reversion of GA-R was about 22 folds. The findings show that the ganoderma triterpene may be good candidates for anti-tumor and anti MDR chemotherapy.

Amplification and expression of a multidrug resistance gene in human glioma cell lines

1990 ◽  
Vol 72 (1) ◽  
pp. 96-101 ◽  
Author(s):  
Tsuyoshi Matsumoto ◽  
Eiichi Tani ◽  
Keizo Kaba ◽  
Nobuo Kochi ◽  
Hideki Shindo ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Cell Lines ◽  
Glioma Cell ◽  
Multidrug Resistant ◽  
Glioma Cell Line ◽  
Cross Resistance ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Glioma Cell Lines

✓ Two human glioma cell lines were examined for multidrug resistance (MDR). A vincristine (VCR)-resistant glioma cell line showed a cross resistance to Adriamycin (doxorubicin, ADR) and etoposide (VP-16) to varying extents, suggesting the presence of MDR; the resistance to VCR was considerably decreased by calcium entry blockers. On the other hand, another VCR-sensitive glioma cell line exhibited no cross resistance to ADR or VP-16. Double minute chromosomes and homogeneously staining regions as well as clonal aberrations of chromosome 7 were not observed in cytogenetic studies of multidrug-resistant and multidrug-sensitive glioma cell lines. In Northern and Southern blot analyses, MDR gene 1 (MDR1) messenger ribonucleic acid (mRNA) was shown to be overexpressed without any amplification of the MDR1 gene in multidrug-resistant glioma cell lines as compared to multidrug-sensitive glioma cell lines. It would be reasonable to suggest that amplification of the MDR1 gene may not be a sine qua non for acquisition of MDR and that the MDR1 mRNA level may be well correlated with the extent of MDR.

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