• Biomolecules & Therapeutics
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• 제17권4호
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• pp.370-378
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• 2009

N-myc downstream-regulated gene 2 (NDRG2) has recently been found to be a tumor suppressor gene. Although it has been reported that NDRG2 expression in breast cancer cells decreases cell proliferation by inhibiting STAT3 activation via SOCS1 induction, the molecular mechanism of chemotherapeutic agent-induced apoptosis is not well known. To elucidate the effect of NDRG2 on the apoptotic pathway induced by doxorubicin, we established stable cell lines expressing NDRG2 and investigated the effect of NDRG2 expression on the doxorubicin-induced apoptosis. While STAT3 activation was remarkably inhibited by NDRG2 overexpression, the expression level of p21 was increased by NDRG2 expression. We confirmed that NDRG2-expressing cells treated with doxorubicin suppressed STAT3 activation and upregulated p21 expression. NDRG2 expression considerably enhanced TUNEL positive apoptotic cells, poly-ADP ribose polymerase (PARP) cleavage, release of cytochrome c to cytosol, and caspase-3 activity in doxorubicin-induced apoptosis. Bid expression in a resting state and after treatment with doxorubicin increased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells. Meanwhile, Bcl-$x_L$ expression decreased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells in a resting state and in doxorubicin-treated cells. Collectively, these data suggest that suppression of STAT3 activation by NDRG2 influences the sensitivity to doxorubicin-induced apoptosis of breast cancer cells and this may provide a potential therapeutic benefit to overcome the resistance against doxorubicin in breast cancer.

• 대한한의학방제학회지
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• 제10권1호
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• pp.131-142
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• 2002

The effect of Banhasasim-tang extracts on the cardiac toxicity and general symptom induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. The changes of body weight, clinical signs, necropsy findings and organ weights of heart were observed. The results were as followed. 1. Decrease of body weight after Doxorubicin treatment were dose-dependently inhibited by Banhasasim-tang extracts. 2. The degrees of anorexia, ataxia and dehydration that were observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. 3. Increase of absolute and relative heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition. the degrees of heart congestion and enlargement were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. In conclusion, the toxicity of Doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of heart) was inhibited and/or prevented by Banhasasim-tang extracts. According to these results. it is considered that Banhasasim-tang has some preventive effect against to toxicity induced by Doxorubicin.

• Molecules and Cells
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• 제37권11호
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• pp.812-818
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• 2014

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.94-103
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• 2024

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

• 생명과학회지
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• 제24권6호
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• pp.700-706
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• 2014

본 연구에서는 anthracycline 계열 항암항생제인 doxorubicin의 암세포 전이 억제 여부를 LNCap 전립선 암세포를 이용하여 이동성 및 침윤성 억제 효능 측면에서 조사하였다. 본 연구의 결과에 의하면 doxorubicin은 LNCap 세포의 이동성과 침윤성을 현저하게 억제시켰으며, matrix metalloproteinase (MMP)-2 및 -9의 발현과 활성을 저해함과 동시에 tissue inhibitor of metalloproteinase (TIMP)-1 및 -2의 발현은 증가시켰다. Doxorubicin은 또한 tight junctions (TJs)의 전기적 저항성을 증대시켰으며, 이는 TJs의 주요 구성인자인 claudin family 인자들의 발현 억제와 연관성이 있었다. 따라서 LNCap 세포에서 doxorubicin에 의한 전이의 억제에는 최소한 TJ의 견고성 증대와 MMPs의 활성 억제가 관여할 것으로 추정된다.

• 대한화학회지
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• 제52권2호
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• pp.118-123
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• 2008

항암제인 독소루비신과 아데닌과의 상호작용을 알아보기 위하여 10-3~10-4의 수용액상 농도 범위에 서 1 : 2의 부피비로 혼합하여 조사하였다. 자외선 공명라만 분광법과 표면증강 라만 분광법을 이용하여 수용 액상에서 독소루비신 분자의 아데닌 분자에 대한 결합 자리를 알아 본 결과 독소루비신 분자는 아데닌 분자 의 7번 위치의 질소와 상호작용 가능성을 확인할 수 있었다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVI)
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• pp.82-85
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• 2005

Doxorubicin is a highly-valuable anthracycline-family polyketide drug with a very potent anticancer activity, typically produced by a Gram-positive soil bacterium called Streptomyces peucetius. Thanks to the recent development of Streptomyces genomics-based technologies, the random mutagenesis approach for Streptomyces strain improvement has been switched toward the genomics-based technologies including the application of DNA microarray systems. In order to identify and characterize the genomics-driven potential target genes critical for doxorubincin overproduction, three different types of doxorubicin overproducing strains, a dnrI(doxorubicin-specific positive regulatory gene)-overexpressor, a doxA (gene involved in the conversion from daunorubicin to doxorubicin)-overexpressor, and a recursively-mutated industrial strain, were generated and examined their genomic transcription profiles using Streptomyces DNA microarray systems. The DNA microarray results revealed several potential target genes in S. peucetius genome, whose expressions were significantly either up- or down-regulated comparing with the wild-type strain. A systematic understanding of doxorubicin overproduction at the genomic level presented in this research should lead us a rational design of molecular genetic strain improvement strategy.

• BMB Reports
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• 제31권1호
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• pp.95-100
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• 1998

Two innovative methods to prepare target-sensitive immunoliposomes containing doxorubicin by coupling monoclonal antibodies (mAb DH2, SH1) specific to cancer cell surface antigens ($G_{M3}$, $Le^X$) have been developed and are described here. Firstly, liposomes containing N-glutaryl phosphatidylethanolamine (NGPE) were prepared, followed by the encapsulation of doxorubicin, DH2 or SH1 antibodies were conjugated to NGPE in the liposomes (direct coupling). Secondly, liposomes were prepared with NGPE/mAb conjugates by the detergent dialysis method (conjugate insertion), and then doxorubicin was encapsulated by proton gradient. The immunoliposomes prepared by both methods were able to specifically bind to the surface of the tumor cells - B16BL6 mouse melanoma cells. The efficiencies of doxorubicin-entrapping into liposomes prepared by direct coupling and conjugate insertion was about 98% and 25%, respectively. These types of liposomal formulation are sensitive to target cells, which can be useful for various clinical applications.

• 대한약침학회지
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• 제20권4호
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• pp.243-256
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• 2017

Doxorubicin as a chemotherapeutic drug is widely used for the treatment of patients with cancer. However, clinical use of this drug is hampered by its cardiotoxicity, which is manifested as electrocardiographic abnormalities, arrhythmias, irreversible degenerative cardiomyopathy and congestive heart failure. The precise mechanisms underlying the cardiotoxicity of doxorubicin are not clear, but impairment of calcium homeostasis, generation of iron complexes, production of oxygen radicals, mitochondrial dysfunction and cell membrane damage have been suggested as potential etiologic factors. Compounds that can neutralize the toxic effect of doxorubicin on cardiac cells without reducing the drug's antitumor activity are needed. In recent years, numerous studies have shown that herbal medicines and bioactive phytochemicals can serve as effective add-on therapies to reduce the cardiotoxic effects of doxorubicin. This review describes different phytochemicals and herbal products that have been shown to counterbalance doxorubicin-induced cardiotoxicity.

• 대한한방종양학회지
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• 제8권1호
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• pp.9-21
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• 2002

Object The effect of Banhasasim-tang extracts on the hepatic, splenic toxicity and induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Method The changes of body weigh, organ weights of liver and spleen were observed with blood GOT and GPT level. Results 1. Increase of absolute and relative liver weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in Doxorubicin treatment group were significantly decreased in Banhasasim-tang extracts dosing groups. 2. Decrease of absolute and relative spleen weight observed in Doxorubicin treatment group were dose dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group.