• Archives of Pharmacal Research
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• v.29 no.10
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• pp.866-873
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• 2006

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.51-55
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• 2016

Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6849-6853
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• 2014

Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.

• The Korean Journal of Nuclear Medicine
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• v.33 no.2
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• pp.152-162
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• 1999

Purpose: To determine whether $^{99m}Tc$-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively $^{99m}Tc$-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular $^{99m}Tc$-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. Materials and Methods: We measured percentage uptake of $^{99m}Tc$-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of $^{99m}Tc$-MIBI were also evaluated with or without overex-pression of mdr1 gene in cultured murine leukemia Ll210 cells. Results: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of $^{99m}Tc$-MIBI was higher in mdr1 negative Ll210 cells than those of mdr1 positive cells, and higher when incubated in $37^{\circ}C$ than $4^{\circ}C$. In the presence of verapamil, cyclosporin or dipyridamole, $^{99m}Tc$-MIBI uptake was increased upto 604% in mdr1 positive cells. Conclusion: Cellular uptake of $^{99m}Tc$-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MBR-reversing agents increase cellular uptake. These results suggest that $^{99m}Tc$-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3309-3315
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• 2016

Helicobacter pylori as the second most common cause of gastric cancer in the world infects approximately half of the developed countries population and 80% of the population living in developing countries. Integrons as genetic reservoirs play major roles in dissemination of antimicrobial resistance genes. To the best of our knowledge, this is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes in H. pylori isolates from Iran. This cross-sectional study was conducted in Tehran among 110 patients with H. pylori infection. Antimicrobial susceptibility testing (AST) for H. pylori strains were assessed by the micro broth dilution method. Class 1 and 2 integrons were detected using PCR. In order to determine gene cassettes, amplified fragments were subjected to DNA sequencing of both amplicon strands. The prevalence of resistance to clarithromycin, metronidazole, clarithromycin, tetracycline, amoxicillin, rifampin, and levofloxacin were 68.2% (n=75), 25.5% (n=28), 24.5% (n=27), 19.1% (n=21), 18.2% (n=20) and 16.4% (n=18), respectively. Frequency of multidrug resistance among H. pylori isolates was 12.7%. Class 2 integron was detected in 50 (45.5%) and class 1 integron in 10 (9.1%) H. pylori isolates. The most predominant gene cassette arrays in class 2 integron-bearing H. pylori were included sat-era-aadA1, dfrA1-sat2-aadA1, blaoxa2 and, aadB whereas common gene cassette arrays in class 1 integron were aadB-aadA1-cmlA6, aacA4, blaoxa2, and catB3. The high frequency of class 2 integron and multidrug resistance in the present study should be considered as a warning for clinicians that continuous surveillance is necessary to prevent the further spread of resistant isolates.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.52 no.6
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• pp.596-604
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• 2019

Vibrio parahaemolyticus causes food poisoning, mainly via marine fisheries products. We investigated the virulence factors and drug resistance of V. parahaemolyticus isolated from fisheries products purchased from the Yeosu Fisheries Market. The isolates were identified using a variety of biochemical tests and the detection of toxR and hns gene. The presence of the virulence factor-encoding genes tdh and trh in the isolates was also investigated by PCR. The resistance of the isolates to 13 antibacterial agents was tested using the disc-diffusion method and carriage of β-lactamase genes and class 1 integrons by ampicillin-resistant isolates was investigated by PCR. Four of seventeen isolates identified as V. parahaemolyticus by biochemical tests produced a species-specific PCR band. Those isolates showed >98% 16S rRNA gene sequence homology with V. parahaemolyticus and only one isolate harbored the tdh gene. All of the V. parahaemolyticus isolates were resistant to ampicillin and amoxicillin; moreover, VPA0477, a class A β-lactamase gene, and class 1 integrons were detected. Therefore, V. parahaemolyticus from fisheries products represents a low risk to human health. Also, V. parahaemolyticus is likely to develop multidrug resistance because it has class 1 integrons.

• Parasites, Hosts and Diseases
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• v.61 no.1
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• pp.78-83
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• 2023

The use of an effective antimalarial drug is the cornerstone of malaria control. However, the development and spread of resistant Plasmodium falciparum strains have placed the global eradication of malaria in serious jeopardy. Molecular marker analysis constitutes the hallmark of the monitoring of Plasmodium drug-resistance. This study included 96 P. falciparum PCR-positive samples from southern Somalia. The P. falciparum chloroquine resistance transporter gene had high frequencies of K76T, A220S, Q271E, N326S, and R371I point mutations. The N86Y and Y184F mutant alleles of the P. falciparum multidrug resistance 1 gene were present in 84.7 and 62.4% of the isolates, respectively. No mutation was found in the P. falciparum Kelch-13 gene. This study revealed that chloroquine resistance markers are present at high frequencies, while the parasite remains sensitive to artemisinin (ART). The continuous monitoring of ART-resistant markers and in vitro susceptibility testing are strongly recommended to track resistant strains in real time.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5619-5625
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• 2012

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.119-124
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• 2022

Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical opportunistic pathogens. Moreover, these bacteria are known to possess multidrug-resistant (MDR) properties. This study investigates the antimicrobial activity of six fermented products, which have varying efficacies against P. aeruginosa, E. coli, and S. aureus. To identify novel candidate genes, differential expression analysis was performed using an annealing control primer. In the disk diffusion method, Fig vinegar (FV) and Diospyros kaki Thunb vinegar (DTV) showed the greatest increase in inhibition compared to other fermented products, whereas fermented Korean traditional nature herb (FKTNH) had no antibacterial effect. This study identified down-regulation of Escherichia coli O157:H7 ompW gene for outer membrane protein W, whereas gene for synthetic construct Lao1 gene for L-amino acid oxidase were up-regulated in E. coli treated with 5% FV. Consuming fermented vinegar helps prevent bacterial infections. Especially, FV and DTV are potentially useful alternative natural products for multidrug resistance. Furthermore, both are expected to be used as effective natural antimicrobial agents, such as disinfectants.

• BMB Reports
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• v.56 no.5
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• pp.302-307
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• 2023

Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. Herein, we demonstrated that rpS3 and Lyn interact with each other, and the phosphorylation of rpS3 by Lyn, causing ribosome heterogeneity, upregulates the translation of p-glycoprotein, which is a gene product of multidrug resistance gene 1. In addition, we found that two different regions of the rpS3 protein are associated with the SH1 and SH3 domains of Lyn. An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation.