• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.47-51
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• 2004

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance Is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By using adriamycin-resistance CL02 cancer cells, we undertook the screening fur agents which were effective to multidrug-resistant cancer cells from strains of the species Sorangium cellulosum isolated in our laboratory. Sorangium cellulose, cellulose-degrading myxobacteria have recently proved to be a rich source of novel anticancer agents. One of the significant examples is the promising anticancer agent epothilone. JW 1006 is the first strain of Sorangium cellulosum which was selected by us for the isolation of a metabolite by a biological screening because of a high cytotoxic activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation of the culture broth led to the Isolation of two active principles, disorazole $A_1$ and $A_2$. They showed potent cytotoxicity against CL02 cancer cells with $IC_{50}$ values in the picomolar range, and were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells.

• Journal of Yeungnam Medical Science
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• v.13 no.1
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• pp.11-21
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• 1996

항암치료에 있어 내성기전은 암세포의 종류에 따라 다양하며 동일세포라도 내성이 생긴 항암제에 따라 그 기능이 다른 것으로 보고되고 있으며 세포종류 및 항암제에 따른 각각의 내성기전을 완전히 알기란 그리 쉬운 일이 아니다. 그러나 임상치료에 있어서 항암제의 적용은 대개 내성 생성이 잘 안되는 즉 교차내성이 적게 일어나는 약제끼리의 선택이 화학요법에 유리하며 재발방지의 지표가 될 수 있으며 내성억제가 가능한 약제의 개발이 중요하다. 또 암에 따른 정확한 내성기전을 잘 밝힘으로서 내성을 방지할 수 있는 target 약제를 함께 병용 개발하는 것이 암의 치료의 지름길이 될 수 있다.

• Journal of Yeungnam Medical Science
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• v.9 no.1
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• pp.75-89
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• 1992

The development of multi drug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell(SNU-1/$Cis_5$) was induced from human stomach cancer cell line(SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/$Cis_5$, We compared the value of $IC_{50}$ - drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNU-1/$Cis_5$ were as follows; vinblastine, > 43.0 ; epirubicin, 22.9 ; dactinomycin, 16.0 ; etoposide, 15.0 ; vincristine, 9.2 ; adriamycin, 5.7 ; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of $10{\mu}M$ verapamil for SNU-1/$Cis_5$ were as follows; vincristine, 13.1 ; epirubicin, 10.0 ; etoposide, 6.3 ; vinblastine, 4.4 ; dactinomycin, 3.6 ; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.

• Microbiology and Biotechnology Letters
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• v.30 no.2
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• pp.157-161
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• 2002

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing adriamycin-resistance CL02 cancer cells, we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW117 was selected for study since the solvent extract of cell mass of the strain was found to exhibit significant activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation led to the isolation of phenalamides $A_2$ and $A_3$. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Phenalamides$ A_1$,$ A_2$ and $A_3$ were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells with $IC_{50}$ values ranging from 0.23~0.57 $\mu\textrm{g}$/ml.

• Journal of Korean Traditional Oncology
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• v.15 no.1
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• pp.119-128
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• 2010

항암치료는 현재 암환자의 주요한 치료임에도 불구하고 항암제내성과 같은 문제점을 가지고 있다. 약물내성은 다양한 기전에 의해 발생하는데 수송단백질의 과발현, 비독성화발현, 손상유전자의 복구, 세포사멸신호의 변화, STAT-3와 NF-${\kappa}B$의 발현 등이 포함된다. 암세포는 저산소환경에서 발생하며 일반세포에 비해 무산소해당에 상대적 의존도가 높고 이는 암세포의 성장과 전이를 촉진하는 인자가 된다. 항암제가 효과를 내기 위해서는 산소가 필요한데 저산소환경은 이를 방해하며 또한 유전자의 불안정화로 인해 약물내성이 유도된다. NF-${\kappa}B$는 주요 전사인자 중 하나로서 각종 염증과 암에서 지속적으로 활성화되며 암세포의 변화, 증식, 침윤, 전이에 관여한다. 환경적 스트레스 등과 대부분의 항암약제들이 NF-${\kappa}B$를 활성화시키며 임상적으로도 암환자의 생존과 연관된 중요한 예후인자이다. NF-${\kappa}B$의 발현은 항암제로 인한 암세포의 자멸을 회피하게 만들고 수송단백질을 활성화시켜 항암제내성을 유도한다. 강황, 적포도, 고추, 건칠 등 다양한 천연물에서 NF-${\kappa}B$를 억제시키는 효능이 발견되었으며 이는 항암제내성을 억제시키고 항암제의 효과를 증대시킨다. 저산소환경의 개선과 NF-${\kappa}B$의 억제는 상호연관성을 가지고 있으며 항암제내성의 개선뿐만 아니라 암치료제 개발의 새로운 연구목표가 될 수 있다.

• The Korean Journal of Applied Statistics
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• v.6 no.2
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• pp.383-391
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• 1993

Interaction between anti-cancer agents and various modulators of multidrug resistance in producing their joint effects are of fundamental interest in the chemtherapeutic treatment of cancer. We generate a dose-response curve for each combination of several anti-cancer agents and modulators based on an in-vitro experiment on each of several human cancer cell lines. We employ a log-linear model developed by Wahrendorf et al (1981) and Piegorsch et al (1988) to detect synergism among several compounds. We show two examples of the data analysis and their results. We believe that these results encourage further experiment in-vivo studies.

• Applied Biological Chemistry
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• v.45 no.2
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• pp.114-118
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• 2002

Phenalamides $A_1{\sim}A_3$ were reisolated as cytotoxic substances from culture broth of Myxococcus stipitatus JW111. The producing strain was isolated from the marine sediment collected off the shore of Geomun Island, Korea. The active principles were extracted from cell mass with acetone and successively purified by silica gel column chromatography, Sephadex LH-20 column chromatography, and finally recycling prep. HPLC. These compounds demonstrated significant cytotoxicity against certain human cancer cells, having $IC_50$ values ranging from 0.23 to 0.50 ${\mu}g/ml$. Moreover, they also inhibited the growth of adriamycin-resistant HCT/ADM human cancer cell line as well as its parent sensitive cell line.

• The Korean Journal of Nuclear Medicine
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• v.37 no.3
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• pp.178-189
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• 2003

Purpose: Cellular uptakes of $^{99m}Tc-sestamibi(MIBI)\;and\;\;^{99m}Tc-tetrofosmin$ into cancer cell lines expressing multidrug resistance(MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. Materials and Methods: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562(Adr) and vincristine-resistant K562(Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at $1{\times}10^6cells/ml$ incubated at $37^{\circ}C$. Radioactivity in supernatants and pellets were measured with gamma well counter. Results: The cellular uptakes of MIBI and tetrofosmin in K562(Adr) and K562(Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562(Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562(Vcr) cells. Coincubation with verapamil resulted in a increase In cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562(Adr) cell by 14.3- and 8-fold and by K562(Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyciosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562(Adr) cell by 44- and 13-fold and by K562(Vcr) cell by 18.8- and 11.8-fold in maximum, respectively Conclusion: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for defecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.

• Journal of Yeungnam Medical Science
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• v.6 no.2
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• pp.195-205
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• 1989

Development of drug resistance in tumors during treatment is a major factor limiting the clinical use of anticancer agents. When tumor cells acquire resistance to anticancer drug, they show cross-resistance to other antitumor agents. In the present study, SNU-1 cell was induced adriamycin $10^{-7}M$ drug resistance, SNU-1/ADR, in vitro culture system. We got the doubling time and number for viability test during 96 hours by MTT assay. To investigate the cross resistance of various anticancer drugs in human stomach cancer cell SNU-1 and SNU-1/ADR. We compared $IC_{50}$ (drug concentration of 50% reduction) and the relative resistance(RR). SNU-1/ADR was expressed multidrug resistant with vinblastine(RR ; 31.62), vincristine(RR ; 29.50), dactinomycin(RR ; 21.37), epirubicin(RR ; 17.78), daunorubicin(RR ; 14.12), adriamycin(RR ; 7.76), and etoposide(RR ; 4.46), and other drugs, 5-fluorouracil, cisplatin, cyclophosphamide, methotrexate, and aclarubicin, have not cross resistant with adriamycin. There was double minute chromosome in SNU-1/ADR by karyotyping although this change was not seen in SNU-1.

• Journal of Life Science
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• v.19 no.8
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• pp.1023-1032
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• 2009

Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, some cancer cells show either partial or complete resistance to TRAIL. Human leukemic K562 and CEM cells also show resistance to TRAIL-induced apoptosis. Novel molecular target and treatment strategies are required to overcome TRAIL resistance of human leukemia cells. Therefore, the purpose of this study was to target key anti-apoptotic molecules deciding TRAIL resistance for sensitization of TRAIL-resistant K562 and CEM cells, and to evaluate the effect of quercetin as a TRAIL sensitizer on these TRAIL-resistant cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in K562 cells by inhibition of the DNA-PK/Akt signaling pathway, which leads to enhancement of TRAIL-mediated activation of caspases and concurrent cleavage of PARP and up-regulation of Bax. The findings suggest that the DNA-PK/Akt signaling pathway plays an essential role in regulating cells to escape from TRAIL-induced apoptosis, and quercetin could act in synergy with TRAIL to increase apoptosis by inhibition of the DNA-PK/Akt signaling pathway, which overcomes TRAIL-resistance of K562 and CEM cells. This study suggests that DNA-PK might interfere with TRAIL-induced apoptosis in human leukemic cells through activation of the Akt signaling pathway.