Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil and cyclosporin A

2014 ◽  
Vol 17 (1) ◽  
pp. 9-17 ◽  
Author(s):  
M. Król ◽  
K.M. Pawłowski ◽  
K. Majchrzak ◽  
J. Mucha ◽  
T. Motyl
Keyword(s):  
Cyclosporin A ◽  
Cell Lines ◽  
Lung Metastases ◽  
Multiple Drug Resistance ◽  
Clinical Problem ◽  
Multiple Drug ◽  
Glycoprotein P ◽  
Membrane Pump ◽  
Over Expression ◽  
Cancer Chemoresistance

Abstract Cancer chemotherapy can fail in many ways. One of the most significant is the development of multiple drug resistance (MDR), which constitutes a serious clinical problem. The development of MDR relates to the expression of a major membrane pump, P-glycoprotein (P-gp). Thus, currently one of the goals of experimental and clinical oncology is to decrease its activity. So far, many different P-gp inhibitors are available, but their efficacy is still questionable and requires further study. The aim of our study was to assess an impact of classical P-gp inhibitors (verapamil and cyclosporin A) in the reversion of multidrug resistance in canine mammary cancer cells. We used two cell lines isolated from mammary tumors and two cell lines isolated from their lung metastases. All of them showed P-gp over-expression confirmed using Real-time rt-PCR, Skan^R screening station and confocal microscopy. The FACS analysis showed that in three of the examined cell lines, treatment with verpamil/cyclosporin A was ineffective to reverse cancer chemoresistance. However, more studies in this field are required.

scholarly journals Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression

2016 ◽  
Vol 39 (2) ◽  
pp. 481-490 ◽  
Author(s):  
Wang Pan ◽  
Qian Wang ◽  
Yi Zhang ◽  
Naishu Zhang ◽  
Jiamin Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Multiple Drug Resistance ◽  
Protein Detection ◽  
Multiple Drug ◽  
Over Expression ◽  
Anti Cancer ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Main Factor

Background/Aims: Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T). Methods: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. Results: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

2008 ◽  
Vol 27 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Lorne J Brandes
Keyword(s):  
Breast Cancer ◽  
Dna Synthesis ◽  
Cancer Cells ◽  
Multiple Drug Resistance ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Multiple Drug ◽  
Glycoprotein P ◽  
Hormetic Effect

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene) is a novel anti-histaminic and chemopotentiating agent that has a hormetic effect on DNA synthesis in MCF (Michigan Cancer Foundation)-7 human breast cancer cells in vitro and stimulates the growth of experimental tumors in rodents. In a prospectively randomized phase three trial (NCIC MA.19), 152 patients who were co-administered DPPE and doxorubicin survived 50% longer ( P < 0.03) than 153 patients who were administered the same dose and schedule of doxorubicin alone. At clinically relevant in vitro concentrations that do not inhibit the P-glycoprotein (P-gp) pump, DPPE selectively sensitizes the cancer cells that express the multiple drug resistance phenotype, making them more susceptible to the cytotoxic effects of chemotherapeutic agents, including anthracyclines and taxanes. Based on its previously demonstrated interaction with histamine at CYP3A4, a P450 that metabolizes arachidonic acid, and its induction of high levels of prostacyclin in the gut of rodents, modulation by DPPE of the intracellular concentration of arachidonate products, such as hydroxyeicosatetraeinoic acids, implicated in increased cancer cell proliferation and metastasis, is postulated.

Role of the MDR-1-Encoded Multiple Drug Resistance Phenotype in Prostate Cancer Cell Lines

1993 ◽  
Vol 150 (5 Part 1) ◽  
pp. 1544-1547 ◽  
Author(s):  
Gerhard Theyer ◽  
Marion Schirmböck ◽  
Therese Thalhammer ◽  
Edward R. Sherwood ◽  
Gerhard Baumgartner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Prostate Cancer Cell Lines ◽  
Mdr 1

The antiproliferative activity of ferrocene derivatives against drug-resistant cancer cell lines: A mini review

2021 ◽  
Vol 21 ◽  
Author(s):  
Li Li ◽  
Lin Ma ◽  
Jian Sun
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Rational Design ◽  
Multiple Drug Resistance ◽  
Cancer Cell Lines ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Ferrocene Derivatives ◽  
Preclinical Trial

: Cancer, a highly heterogeneous disease at intra/inter patient levels, remains a serious health problem contributing to significant morbidity and mortality worldwide. Despite great progress in clinical treatment, the concerns impeding the success of conventional cancer chemotherapy is descending efficacy of anticancer agents due to the development of drug resistance especially multiple drug resistance (MDR). Ferrocene derivatives have a different mode of action to the platinum anticancer drugs, and the ferrocene-phenol hybrid ferrocifen exhibits potential activity against drug-resistant cancers. Currently, ferrocifen is in preclinical trial, demonstrating that ferrocene derivatives are useful scaffolds for the development of novel anticancer candidates which are active against drug-resistant cancers. In the present review, the current scenario of ferrocene derivatives including ferrocene metal complexes, hybrids and other derivatives with antiproliferative potential against drug-resistant cancer cell lines is summarized for further rational design.

scholarly journals Evaluation of Prognostic Factors, including Duodenal P-Glycoprotein Expression, in Canine Chronic Enteropathy

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2315
Author(s):  
Marco Pietra ◽  
Giorgia Galiazzo ◽  
Francesca Bresciani ◽  
Maria Morini ◽  
Sara Licarini ◽  
...  
Keyword(s):  
Multiple Drug Resistance ◽  
Previous Treatment ◽  
Response To Treatment ◽  
Multiple Drug ◽  
Laboratory Findings ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Single Center Study ◽  
Membrane Bound ◽  
Duodenal Biopsies

The aim of this retrospective single-center study was to evaluate which factors, including expression of P-glycoprotein (P-gp), a membrane-bound protein involved in multiple drug resistance, could predict the response to treatment in canine immunosuppressant-responsive enteropathy (IRE). Dogs with IRE or non-responsive enteropathy (NRE) that were examined from 2005 to 2014 were included and were divided into two groups (IRE vs. NRE). Signalment, history, and clinical and laboratory findings were collected. P-glycoprotein immunohistochemistry was carried out on duodenal biopsies of both groups stored in our biobank, and immunophenotyping and molecular clonality were performed on the NRE samples. Ninety-two dogs were enrolled, 73 IRE (79.3%) and 19 NRE (20.7%), with a prevalence of pure breed (78.3% vs. 21.7%) and male dogs (p < 0.001). Factors associated with a worse prognosis were previous treatment with steroids (p = 0.033) and lower serum total protein concentration (p = 0.005). Clonality testing on the NRE duodenal biopsies showed 5/16 clonal responses, assuming a latent undiagnosed lymphoma as a possible cause of the NRE.

scholarly journals Molecular Basis of Cancer Pain Management: An Updated Review

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 584 ◽  
Author(s):  
V. Subramaniam ◽  
Salem Yehya ◽  
Oon
Keyword(s):  
Pain Management ◽  
Cancer Pain ◽  
Negative Impact ◽  
Multiple Drug Resistance ◽  
Drug Effects ◽  
Individual Variability ◽  
Multiple Drug ◽  
Cancer Pain Management ◽  
Glycoprotein P ◽  
Pain Pathways

Pain can have a significantly negative impact on the quality of life of patients. Therefore, patients may resort to analgesics to relieve the pain. The struggle to manage pain in cancer patients effectively and safely has long been an issue in medicine. Analgesics are the mainstay treatment for pain management as they act through various methods on the peripheral and central pain pathways. However, the variability in the patient genotypes may influence a drug response and adverse drug effects that follow through. This review summarizes the observed effects of analgesics on UDP-glucuronosyl (UGT) 2B7 isoenzyme, cytochrome P450 (CYP) 2D6, μ-opioid receptor μ 1 (OPRM1), efflux transporter P-glycoprotein (P-gp) and ATP-binding cassette B1 ABCB1/multiple drug resistance 1 (MDR1) polymorphisms on the mechanism of action of these drugs in managing pain in cancer. Furthermore, this review article also discusses the responses and adverse effects caused by analgesic drugs in cancer pain management, due to the inter-individual variability in their genomes.

Different Mechanisms of Multiple Drug Resistance in Two Human Leukemic Cell Lines

1988 ◽  
pp. 211-222 ◽  
Author(s):  
WILLIAM T. BECK ◽  
MARY K. DANKS ◽  
JOHN M. ZAMORA ◽  
MARGARET C. CIRTAIN ◽  
JACK C. YALOWICH
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Multiple Drug Resistance ◽  
Leukemic Cell ◽  
Multiple Drug ◽  
Human Leukemic Cell ◽  
Leukemic Cell Lines

The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2)

2000 ◽  
Vol 113 (11) ◽  
pp. 2011-2021 ◽  
Author(s):  
T. Litman ◽  
M. Brangi ◽  
E. Hudson ◽  
P. Fetsch ◽  
A. Abati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Multiple Drug Resistance ◽  
Human Colon ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Multiple Drug ◽  
Resistant Phenotype ◽  
P Glycoprotein ◽  
Mcf 7

Mechanisms of drug resistance other than P-glycoprotein are of increasing interest as the list of newly identified members of the ABC transport family has grown. We sought to characterize the phenotype of the newly discovered ABC transporter encoded by the mitoxantrone resistance gene, MXR, also known as ABCP1 or BCRP. The pharmacodynamics of mitoxantrone and 12 other fluorescent drugs were evaluated by confocal microscopy in four multidrug-resistant human colon (S1) and breast (MCF-7) cancer cell lines. We utilized two sublines, MCF-7 AdVp3000 and S1-M1-80, and detected overexpression of MXR by PCR, immunoblot assay and immunohistochemistry. These MXR overexpressing sublines were compared to cell lines with P-glycoprotein- and MRP-mediated resistance. High levels of cross-resistance were observed for mitoxantrone, the anthracyclines, bisantrene and topotecan. Reduced levels of mitoxantrone, daunorubicin, bisantrene, topotecan, rhodamine 123 and prazosin were observed in the two sublines with high MXR expression. Neither the P-glycoprotein substrates vinblastine, paclitaxel, verapamil and calcein-AM, nor the MRP substrate calcein, were extruded from MCF-7 AdVp3000 and S1-M1-80 cells. Thus, the multidrug-resistant phenotype due to MXR expression is overlapping with, but distinct from, that due to P-glycoprotein. Further, cells that overexpress the MXR protein seem to be more resistant to mitoxantrone and topotecan than cells with P-glycoprotein-mediated multidrug resistance. Our studies suggest that the ABC half-transporter, MXR, is a potent, new mechanism for conferring multiple drug resistance. Definition of its mechanism of transport and its role in clinical oncology is required.

scholarly journals Multiple drug resistance in Candida albicans.

1995 ◽  
Vol 42 (4) ◽  
pp. 497-504 ◽  
Author(s):  
R Prasad ◽  
S K Murthy ◽  
V Gupta ◽  
R Prasad
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Pleiotropic Drug Resistance ◽  
Multidrug Resistance Gene ◽  
Hydrophobic Region ◽  
Membrane Pump ◽  
Collateral Sensitivity ◽  
Sensitivity Pattern

By functional complementation of a PDR 5 (pleiotropic drug resistance) null mutant of S. cerevisiae, we have recently cloned and sequenced a multidrug resistance gene CDR 1 (Candida Drug Resistance). Transformation by CDR 1 of a PDR 5 disrupted host hypersensitive to cycloheximide and chloramphenicol resulted in resistance to these as well as other unrelated drugs. The nucleotide sequence of CDR 1 revealed that, like PDR 5, it encodes a putative membrane pump belonging to the ABC superfamily. CDR 1 encodes a protein of 169.9 kDa whose predicted structural organisation is characterised by two homologous halves, each comprising a hydrophobic region, with a set of six transmembrane stretches, preceded by a hydrophilic binding fold. We now have evidence to suggest that there are several PDR homologues present in C. albicans which display multidrug resistance and a collateral sensitivity pattern different from PDR 5 and CDR 1. The functions of such genes and their products in the overall physiology of C. albicans is not yet established.

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