scholarly journals The Effects of TiO2 Nanoparticles on Cisplatin Cytotoxicity in Cancer Cell Lines

2020 ◽  
Vol 21 (2) ◽  
pp. 605 ◽  
Author(s):  
Basma Salama ◽  
El-Said El-Sherbini ◽  
Gehad El-Sayed ◽  
Mohamed El-Adl ◽  
Koki Kanehira ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Titanium Dioxide Nanoparticles ◽  
Membrane Receptors ◽  
Multi Drug Resistance ◽  
A431 Cells ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Low Expression

There have been many studies on improving the efficacy of cisplatin and on identifying safe compounds that can overcome multi-drug resistance (MDR) acquired by cancer cells. Our previous research showed that polyethylene glycol-modified titanium dioxide nanoparticles (TiO2 PEG NPs) affect cell membrane receptors, resulting in their aggregation, altered localization and downregulation. TiO2 PEG NPs may affect P-glycoprotein (P-gp), a membrane efflux channel involved in MDR. In this study, we investigated the effect of TiO2 PEG NPs on cisplatin cytotoxicity. We used HepG2 cells, which highly express P-gp and A431 cells, which show low expression of P-gp. The results showed that 10 µg/mL 100 nm TiO2 PEG NPs increased intracellular cisplatin levels and cytotoxicity in HepG2 cells but not in A431 cells. TiO2 PEG NPs treatment decreased the expression level of P-gp in HepG2 cells. Our findings indicate that TiO2 PEG NPs enhance cisplatin cytotoxicity by down regulating P-gp and that TiO2 PEG NPs are promising candidates for inhibiting P-gp and reversing drug resistance acquired by cancer cells.

scholarly journals Overcoming P-Glycoprotein-Mediated Doxorubicin Resistance

2021 ◽  
Author(s):  
Suree Jianmongkol
Keyword(s):  
Cancer Cells ◽  
Multi Drug Resistance ◽  
Therapeutic Success ◽  
Glycoprotein P ◽  
Target Delivery ◽  
Doxorubicin Treatment ◽  
Doxorubicin Resistance ◽  
P Glycoprotein ◽  
Strategic Approach ◽  
Effective Level

Intracellular concentration of doxorubicin in target cancer cells is a major determinant of therapeutic success of doxorubicin-based regimens. As known, doxorubicin is a substrate of P-glycoprotein (P-gp), the drug efflux transporter in the ABC superfamily. High expression level of P-gp in cancer cells can prevent intracellular accumulation of doxorubicin up to its effective level, leading to doxorubicin resistance and treatment failure. Moreover, these P-gp-overexpressed cells display multi-drug resistance (MDR) phenotype. Regarding this, application of P-gp modulators (suppressor of P-gp activity and expression) is likely to reverse MDR and restore cell sensitivity to doxorubicin treatment. In searching for potential chemo-sensitizer against resistant cancer, a number of phytochemicals or dietary compounds have been studied extensively for their P-gp modulating effects. Furthermore, combination between doxorubicin and P-gp modulators (e.g., plant-derived compounds, siRNA) given through specific target delivery platforms have been an effective strategic approach for MDR reversal and restore doxorubicin effectiveness for cancer treatment.

PKD2 mediates multi-drug resistance in breast cancer cells through modulation of P-glycoprotein expression

2011 ◽  
Vol 300 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Jiao Chen ◽  
Libing Lu ◽  
Yun feng ◽  
Hui Wang ◽  
Lila Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Multi Drug Resistance ◽  
P Glycoprotein

scholarly journals S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

2021 ◽  
Vol 22 (17) ◽  
pp. 9286
Author(s):  
Laura Mosca ◽  
Martina Pagano ◽  
Luigi Borzacchiello ◽  
Luigi Mele ◽  
Annapina Russo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Defense Mechanism ◽  
Multiple Drug Resistance ◽  
Nutritional Supplement ◽  
Multi Drug Resistance ◽  
Multiple Drug ◽  
Cell Defense ◽  
P Glycoprotein

Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.

scholarly journals Identification of multi-drug resistance gene (MDR1) in equine ileum

2006 ◽  
Vol 36 (1) ◽  
pp. 298-300
Author(s):  
Cláudio Corrêa Natalini ◽  
Renata Lehn Linardi
Keyword(s):  
Drug Resistance ◽  
Mdr1 Gene ◽  
Multi Drug Resistance ◽  
Drug Elimination ◽  
Glycoprotein P ◽  
Future Studies ◽  
Normal Tissues ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
The Impact

P-glycoprotein (P-gp) is a membrane transporter encoded in the Multi-drug Resistance (MDR1) gene expressed in several normal tissues and over expressed in tumor cells. P-gp was already identified in different species but not yet in equine. MDR1 gene and P-gp are able to interfere with bioavailability and disposition of several drugs, altering pharmacokinetic and pharmacodinamic of drugs. The presence of the MDR1 and P-gp in the central nervous system blocks the entry of certain drugs in this tissue and reduces drug absorption and enhances drug elimination when P-gp and MDR1 are presented in the gastrointestinal tract. This study showed that the MDR1 gene is present in equine ileum. Future studies on the impact of the P-glycoprotein encoded gene MDR1 on drugs pharmacologic effects in horses are granted.

Unsymmetric dihydropyridines bearing 2-pyridyl methyl carboxylate as modulators of P-glycoprotein; synthesis and biological evaluation in resistant and non-resistant cancer cells

2019 ◽  
Vol 97 (8) ◽  
pp. 603-614
Author(s):  
Maryam Nejati ◽  
Hossein Sadeghpour ◽  
Sara Ranjbar ◽  
Katayoun Javidnia ◽  
Najmeh Edraki ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Multi Drug Resistance ◽  
Glycoprotein P ◽  
Glycoprotein Synthesis ◽  
Human Cancer Cells ◽  
P Glycoprotein ◽  
Mdr Reversal

Multi-drug resistance (MDR) in cancer cells is often associated with overexpression of P-glycoprotein (P-gp or ABCB1 or MDR1); therefore, modulators of this transporter might be helpful in overcoming MDR. In this study, 16 novel unsymmetrical dihydropyridine (DHP) derivatives bearing 2-pyridyl methyl carboxylate at C3 and a nitroimidazole or nitrophenyl ring at C4 positions of the DHP ring were synthesized. Their cytotoxicity was tested against four human cancer cells by MTT assay. The reversal capacity of MDR was examined in P-gp overexpressing cells (MES-SA/DX5) by measuring the alteration of doxorubicin’s IC50 and performing flow cytometric determination of intracellular rhodamine 123 accumulation. The calcium channel blocking (CCB) activity, as a side effect of DHPs, was tested on the ileum of a guinea pig. Molecular docking was performed to explain the binding mode of compounds. Two derivatives, 4a and 4c, containing 4-nitrophenyl at C4 and possessing methyl (4a) and iso-propyl (4c) carboxylates at the C5 position of DHP core demonstrated superior cytotoxic and MDR reversal activities and lower CCB effect. Docking analysis confirmed the importance of the 4-nitrophenyl ring for P-gp inhibitory activity. Some of the synthesized DHP derivatives with considerable MDR reversal capacity could be promising compounds for further discovery of useful agents for management of drug resistant cancer.

The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation

2013 ◽  
Vol 319 (7) ◽  
pp. 1013-1027 ◽  
Author(s):  
Jasna Banković ◽  
Jörg Andrä ◽  
Nataša Todorović ◽  
Ana Podolski-Renić ◽  
Zorica Milošević ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance ◽  
Cationic Peptide ◽  
P Glycoprotein ◽  
Resistance Modulation

Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies

2016 ◽  
Vol 20 (28) ◽  
pp. 2971-2982
Author(s):  
Cristina Mambet ◽  
Mihaela Chivu-Economescu ◽  
Lilia Matei ◽  
Mihai Stoian ◽  
Coralia Bleotu
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance

Valproic Acid (VPA) in Combination with Knockdown of AKT3 and PI3KCA Genes Inhibits Proliferation, Induces Apoptosis and Autophagy in T98G and U87MG Glioblastoma Multiforme Cells

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Paul-Samojedny M ◽  
◽  
Liduk E ◽  
Borkowska P ◽  
Kowalczyk M ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Drug Resistance ◽  
Glioblastoma Multiforme ◽  
Cell Viability ◽  
Transfection Efficiency ◽  
Effective Control ◽  
Multi Drug Resistance ◽  
U87mg Cell ◽  
Glycoprotein P ◽  
Human Gbm

Purpose: Glioblastoma Multiforme (GBM) is a heterogenous and highly vascularized brain tumor that avoid apoptosis due to P-glycoprotein (P-gp) mediated multi-drug resistance. Therefore, development of new therapeutic strategies that induce apoptosis, inhibit proliferation, and overcome multi-drug resistance is urgently warranted. We examined the efficacy of combination of Valproic Acid (VPA) and knockdown of AKT3 and PI3KCA genes in human glioblastoma T98G and U87MG cell lines. Material and Methods: T98G and U87MG cells were transfected with AKT3 or PI3KCA siRNAs. Transfection efficiency was assessed using Flow Cytometry (FC) and fluorescence microscopy. The influence of AKT3 and PI3KCA siRNAs in combination with VPA on T98G and U87MG cell viability, proliferation, apoptosis and autophagy was evaluated as well. Alterations in the mRNA expression of apoptosis-related genes (CASP3 and Bid) were analyzed using QRT-PCR. Results: The transfection of T98G and U87MG cells with AKT3 or PI3KCA siRNAs and exposition on VPA led to a significant reduction in cell viability, the accumulation of subG1-phase cells and a reduced fraction of cells in the S and G2/M phases, apoptosis or necrosis induction and induction of autophagy. Conclusions: The siRNA-induced AKT3 and PI3KCA mRNA knockdown in combination with VPA may offer a novel therapeutic strategy to more effective control the growth of human GBM cells. Thus, knockdown of these genes in combination with valproic acid inhibits proliferation, induces apoptosis and autophagy in T98G and U87MG cells, but further studies are necessary to confirm a positive phenomenon for the treatment of GBM.

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