• Asian Pacific Journal of Cancer Prevention
• /
• 제17권1호
• /
• pp.51-55
• /
• 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.

• Journal of Microbiology and Biotechnology
• /
• 제20권6호
• /
• pp.1042-1052
• /
• 2010

Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. The presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of the S. Typhimurium strains were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulfonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%), and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%), and cephalexin (17.0%). Resistance genes, $bla_{TEM}$, strA, aadA, sul1, sul2, tetA, tetB, and tetC, were detected among the drug-resistant strains. Thirtythree strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1, and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1-6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem, and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권16호
• /
• pp.6849-6853
• /
• 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.

• 대한핵의학회:학술대회논문집
• /
• 대한핵의학회 2001년도 제40차 춘계학술대회 및 연수교육
• /
• pp.66-75
• /
• 2001

Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

• Journal of Life Science
• /
• 제9권1호
• /
• pp.40-44
• /
• 1999

Glutathione S-transferase (GST) is a multifunctional protein that catalyzes the catalyzes the conjugation of glutathione with electrophilic compounds. It exists in a variety of isoenzy-matic froms with a wide range of substrate specificity and plays a pivotal role in detoxification of various drugs. In order to elucidate the GST-${\pi}$'s involvement of multidrug resistance (MDR) in drug-resistant tumor cell lines, we determined GST-${\pi}$ content by "1 step sandwich method". Consequently, adriamycin resistant cells of MCF-7 (MCF-7/ADM) have 7-fold increase of GST-${\pi}$ content than that of MCF-7 cells, while its {TEX}$IC_{50}${/TEX} was 116-fold greater than parent cell line. By northrn blotting, we compared whether MCF-7/ADM cells express GST-${\pi}$ mRNA. The GST-${\pi}$ mRNA expression in these cells was not inducible, but constitutive when treated for 24 h with a concentration of 0, 20, 200, and 2000 nM of adriamycin, respectively. Taken together, these results suggest that GST-${\pi}$ may not be directly associated with multidrug resistance in these human cancer cell lines.ell lines.

• 생약학회지
• /
• 제28권4호
• /
• pp.174-178
• /
• 1997

Methanol extracts from 450 plants were screened for muttidrug-resistance reversing activity using drug sensitive KB-3-1 and multidrug-resistant KB-Vl cells. Among them, the extracts of Cynanchum wilfordii, Torilis japonica, Celastrus orbiculatus, Melia toosendan and Teminialia chebula strongly potentiated vinblastine cytotoxicity in KB-Vl cells. But their cytotoxicities to both sensitive KB-3-1 and resistant KB-Vl cells were in the same order of magnitude. These results indicate that the above samples would contain the active principles which do not exert their ativity solely by cytotoxicity.

• 한국미생물학회:학술대회논문집
• /
• 한국미생물학회 2009년도 International Meeting of the Microbiological Society of Korea
• /
• pp.68-69
• /
• 2009

• Archives of Pharmacal Research
• /
• 제29권11호
• /
• pp.1018-1023
• /
• 2006

Chemoresistance remains the major obstacle to successful therapy of cancer. In order to understand the mechanism of multidrug resistance (MDR) that is frequently observed in lung cancer patients, here we studied the contribution of MDR-related proteins by establishing lung cancer cell lines with acquired resistance against etoposide. We found that human H460 lung cancer cells responded to etoposide more sensitively than A549 cells. Among MDR-related proteins, the expression of p-glycoprotein (Pgp) and lung resistance protein (LRP) were much higher in A549 cells compared with that in H460 cells. When we established H460-R1 and -R2 cell lines by progressive exposure of H460 cells to increasing doses of etoposide, the response against etopbside as well as doxorubicin was greatly reduced in R1 and R2 cells, suggesting MDR induction. Induction of MDR was not accompanied by a decrease in the intracellular accumulation of etoposide and the expression of MDR-related proteins that function as drug efflux pumps such as Pgp and MRP1 was not changed. We found that the acquired resistance paralleled an increased expression of LRP in H460 cells. Taken together, our data suggest the implicative role of LRP in mediating MDR in lung cancer.

• Archives of Pharmacal Research
• /
• 제19권5호
• /
• pp.342-347
• /
• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.

• 대한임상검사과학회지
• /
• 제50권4호
• /
• pp.431-437
• /
• 2018

Acinetobacter baumannii는 광범위한 항생제에 대한 저항성으로 인해 감염된 환자의 사망률이 높아지는 적색 경보 병원체로 분류됩니다. 이 연구에서 다제 내성 A. baumannii(MRAB)의 18가지 임상 분리 균주에 대해 일부 에센셜 오일(티트리, 로즈마리, 라벤더 오일)의 항균 활성을 평가하고자 하였다. Carbapenemase 선별을 위한 Hodge 시험법은 A. baumannii의 20 가지 균주가 모두 imipenem에 내성이 있음을 보여주었습니다. 다제 내성 미생물의 확인은 VITEK 시스템을 통해 수행하였다. 에센셜 오일의 항균 활성은 MRAB에 대한 디스크 확산 방법으로 평가하였다. 디스크 확산 방법에서 tee tree는 라벤더 오일에 비해 억제 크기가 가장 크게 증가했으며, 로즈마리는 항균 효과가 없었다. 티 트리 오일은 가장 일반적인 인간 병원균 및 MRAB 감염의 치료 및 예방을 위한 대체 천연 제품으로 유용할 것으로 보인다. 따라서 이 연구의 결과는 다제 내성 A. baumannii의 항균 효과를 입증했으며, 미래에 천연 에센셜 오일을 사용하는 손 소독제와 같은 항균제로 사용될 것으로 예상됩니다.