• Journal of Nutrition and Health
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• 제36권8호
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• pp.828-833
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• 2003

Dially disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventive activity against various cancers. In this study, the synergistic effect of DADS and daunorubicin on the cytotoxicity of HL-60 cells, a human leukemia cell line, was investigated. DADS at 25 M greatly potentiated daunorubicin-induced cell death, decreasing cell viabilityto50%ofthe control. Daunorubicin-induced apoptosis was accompanied by the activation of caspase-3, the degradation of poly-(ADP-ribose) polymerase (PARP) and D4-GDI, and DNA fragmentation, which were blocked by pre-treatment with acetyl-Asp-Glu-Val-Asp- dialdehyde (Ac-DEVD-CHO). Treatment that combined 25 M DADS and 100 nM daunorubicin caused a similar degree of caspase-3 activation, PARP and D4-GDI degradation, and DNA fragmentation to that caused by treatment with 250 nM daunorubicin alone. These results indicate that combined therapy using daunorubicin with DADS, a component of food, and garlic can effectively decrease the therapeutic dose of daunorubicin, preventing the severe side effects of daunorubicin.

• 한국환경성돌연변이발암원학회지
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• 제19권2호
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• pp.112-115
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• 1999

The action mechanism of the inhibitory effect of some natural products on the DNA strand break and DNA damage was investigated in vitro and in vivo. In the E. coli chromosomal DNA strand break experiment in vitro, three mushroom water extracts were effective on the DNA strand breaking by daunorubicin. Phellinus linteus water extract inactivated daunorubicin, a DNA strand breaking agent, but did not protect DNA from daunorubicin-induced DNA strand breaking. Agaricus blazei water extract inhibited DNA strand breaking action of daunorubicin not only by daunorubicin inactivation, but also by DNA protection from daunorubicin. An inhibitory effect of Ganoderma lucidum water extract on the DNA strand break was based on the DNA protection rather than daunorubicin inactivation. In vivo mutagen assay system (SOS-chromotest), among three mushroom water extracts Phellinus linteus water extract was the most effective one on the inhibition of DNA damage by 4-NQO. The results suggest that all three mushroom water extracts inhibit daunorubicin-induced DNA damage and in vivo DNA damaging action of 4-NQO by the reaction of mutagen inactivation or DNA protection from the mutagen.

• Preventive Nutrition and Food Science
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• 제7권2호
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• pp.128-132
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• 2002

The present study was performed to observe the role of protein kinase C (PKC) inhibitors (H-7, staurosporine) and daunorubicin in the cell death process of MCF7 cells; and examined whether or not the type of induced cell death was apoptosis. The usefulness of the combined therapy of PKC inhibitors and daunorubicin to improve the adverse effect of daunorubicin was also investigated. Cell death was induced by treatment with PKC inhibitors or daunorubicin. Characteristic morphologic features of cell shrinkage, chromatic condensation, and cytoplasmic vacuolization were observed. These treatments also stimulated the cleavage of poly-(ADP-ribose) polymerase (PARP), an early event in apoptosis. With slight differences in the percentage of apoptosis-induced cells, staurosporine, H-7 and daunorubicin effectively induced apoptosis in MCF7 cells. Furthermore, combined treatment of PKC inhibitors and daunorubicin significantly drove the cells into an apoptotic state. Hence, our results revealed the possible therapeutic value of combined therapy for the prevention of drug resistance and adverse side effects.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• Journal of Pharmaceutical Investigation
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• 제40권5호
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• pp.269-275
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• 2010

P-gp plays a critical role in drug disposition and represents a mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to inhibit P-gp. Therefore, the aim of this study was to identify new candidate chemosensitizers by screening various plant extracts. The ability of natural plant extracts to inhibit P-gp activity was assessed by measuring cellular accumulation of calcein AM, daunorubicin and vincristine in P-gp overexpressing MDCKII-MDR1 cells. Among more than 800 plant extracts, eight were found to inhibit P-gp activity. Curcuma aromatica extract produced greatest inhibition, followed by Curcuma longa and Dalbergia odorifera extracts. Extracts of Aloe ferox, Curcuma zedoariae rhizome, Zanthoxylum planispinum, and Ageratum conyzoides showed moderate inhibitory effects. Curcumin and quercetin exhibited similar inhibition of P-gpmediated efflux of daunorubicin and vincristine, and flavones had a lesser effect. When chemosensitizing effect was evaluated by measuring daunorubicin sensitivity to MDCKII-MDR1 cells in the presence of natural plant extracts, Curcuma aromatica showed the most potent chemosensitizing effect based on daunorubicin cytotoxicity. In conclusion, natural plant extracts such as Curcuma aromatica can potently inhibit P-gp activity and may have potential as a novel chemosensitizers.

• 대한화학회지
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• 제30권1호
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• pp.109-117
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• 1986

항암항생제 Daunorubicin(2a)합성단계의 최종물질인 7,9-Dideoxydaunomycinone (32)를 3-methoxybenzoic acid(5)로 부터 합성하였다. 3-methoxybenzoic acid를 4-methoxy-3-(phenylsulfonyl)-1(3H)-isobenzofuranone(11)으로 변형시킨 뒤 Hauser와 Rhee가 개발한 고리접합법을 이용하여 trimethoxynaphthoate 16을 얻은 후에 phenylsulfonylnaphthofuranone 22로 변화시킨 뒤 이 물질을 7-(ethylenedioxy)-2-octenoate(23)과 Michael형태의 반응을 전개시켜 anthracenoate 24를 얻었다. Anthracenoate을 tetracyclic 화합물 28로 바꾼뒤 ring B와 C에 붙은 methyl기들을 제거하여 7,9-Dideoxydaunomycinone(32)를 만들었다.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.131-137
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• 1994

Drug delivery system by the use of red blood cells was established to sustain the release of drugs in the circulatory system by the intravenous injection. The entrapment method by the preswelling technique was re-examined and evaluated for searching the new entrapping conditions without hemolysis. The addition of 4 volume of $0.6{\times}\;hank's$ balanced salt solution (HBSS) into 1 volume of 50% red blood cells suspension did not induce the hemolysis and change the hematocrit level in this experimental condition (within 15 min). Most of daunorubicin could be entrapped into red blood cells within 15 min. While the intracellular adenosine triphosphate (ATP) level followed by the entrapment was reduced to 86% of normal ATP level, the membrane fluidity and the shape factor of red blood cells were not altered. The release rate of daunorubicin from red blood cells was affected by the hemolysis under this condition. To maintain the intracellular ATP in red blood cells, the new reaction buffer was made With the addition of ATP and sodium pyruvate during the entrapment procedure because the hemolysis during the release test would reflect the loss of intracellular ATP that might result in the decrease of the viability in vivo. The addition of ATP raised the intracellular ATP level, which protect the hemolysis during the release test.

• 약학회지
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• 제40권2호
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• pp.117-125
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• 1996

3'-Deamino-3-hydroxy-4'-fluoro- or 3'-deamino-3'-hydroxy-4'-azido-daunorubicin(6,8) and -doxorubicin(7,9) have been synthesized, respectively. Compounds 7,8 and 9 were mo re cytotoxic than daunorubicin(1) and doxorubicin(2) against L1210 murine leukemic cell in vitro. When administered intraperitoneally for 9 days starting 1 day after tumor inoculation, compounds 7(T/C 605%) and 9(T/C 488%) showed significant antitumor activity for ip-inoculuated L1210 murine leukemia at wide range of doses.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1999년도 공동 춘계학술대회
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• pp.71.2-71
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• 1999

No Abstract, See Full Text

• Journal of Yeungnam Medical Science
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• 제9권1호
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• pp.75-89
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• 1992

복합약제내성암세포주의 출현은 암의 화학 요법에 있어서 중요한 문제점중의 하나이며 이 복합내성 암세포의 출현에 대한 정확한 기전은 아직 밝혀져 있지 않다. 본 실험에서는 약제내성 암세포의 다른 항암제에 대한 복합내성 형성정도와 calcium 길항제인 verapamil에 의한 내성극복 정도를 비교하고 내성 암세포의 세포막 단백질의 변화를 관찰하였다. 사람의 위암 세포주 SNU-1을 cisplatin 농도 $0.001{\mu}M$에서 시작하여 $10{\mu}M$까지 증가시켜 내성세포 SNU-1/$Cis_5$를 얻었으며, MTT assay로 세포성장을 관찰한 결과 doubling time은 SNU-1이 약 29 시간, SNU-1/$Cis_5$는 약 38시간으로 내성세포가 감수성세포보다 성장속도가 느린 것을 관찰하였다. 약제 감수성 검사를 위해서 4일간의 MTT assay로 대조군에 대한 50% 세포 생존시의 약제농도 $IC_{50}$를 비교하여 상대적 내성도 (Relative Resistance, RR)를 측정하였는데 cisplatin, 81.4; vinblastine, > 43.0; epirubicin, 22.9 ; dactinomycin, 16.0 ; etoposide, 15.0 ; vincristine, 9.2 ; adriamycin, 5.7 ; aclarubicin, 5.3으로 관찰되었고 그외의 약제인 cyclophosphamide, 5-fluorouracil, methotrexate, daunorubicin에서는 낮게 나타났다. $10{\mu}M$의 verapamil에 의한 내성 억제 효과는 vincristine, 13.1 ; epirubicin, 10.0 ; etoposide, 6.3 ; vinblastine, 4.4 ; dactinomycin, 3.6 ; daunorubicin, 2.4로 나타났다. Radioiodination을 이용한 SDS-PAGE로 SNU-1/$Cis_5$에서 항암제 내성과 관련된 것으로 여겨지는 51,400와 81,300 dalton의 막단백질의 발현을 관찰하였다.