• Journal of the Korean Chemical Society
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• v.47 no.3
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• pp.257-264
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• 2003

This study has investigated the temperature-sensitive liposomes, which release anticancer drug(doxorubicin) at the hyperthermia temperature$(~40^{\circ}C)$. The temperature-sensitive liposomes were modified with a copolymers of N-isopropylacrylamide(NIPAAm) and acrylamide(AAm), which exhibit a lower critical solution temperature (LCST) at the hyperthermia temperature. The release of doxorubicin from the modified liposomes was determined by measuring the fluorescence intensity with changing temperature and time. The release of doxorubicin from liposomes modified with poly(NIPAAm-co-AAm) copolymer was increased significantly, because poly(NIPAAm-co-AAm) could undergo the conformational transition in the narrow hyperthermia temperature region$(~40{\pm}2^{\circ}C)$. Moreover, we observed that doxorubicin released from liposomes within 5 minutes, and the size of modified liposomes was 120~170 nm. In this study, we have prepared temperature-sensitive liposomes which could be controlled by temperature. They can be applied in the field of a drug delivery system for tumor targeting by temperature control.

• Herbal Formula Science
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• v.12 no.1
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• pp.131-148
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• 2004

In order to evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilkitang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Bojungikkeehapdaechilkitang with their concomitant treatment against 3LL(Lewis lung carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to 3LL cell lines. Bojungikkeehapdaechilkitang has only mimic direct anti-tumor effect against to 3LL cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Bojungikkeehapdaechilkitang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and Bojungikkeehapdaechilkitang extracts.

• Molecules and Cells
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• v.39 no.2
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• pp.129-135
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• 2016

Eukaryotic translation initiation factor 2 alpha ($eIF2{\alpha}$), which is a component of the eukaryotic translation initiation complex, functions in cell death and survival under various stress conditions. In this study, we investigated the roles of $eIF2{\alpha}$ phosphorylation in cell death using the breast cancer cell lines MCF-7 and MCF-7/ADR. MCF-7/ADR cells are MCF-7-driven cells that have acquired resistance to doxorubicin (ADR). Treatment of doxorubicin reduced the viability and induced apoptosis in both cell lines, although susceptibility to the drug was very different. Treatment with doxorubicin induced phosphorylation of $eIF2{\alpha}$ in MCF-7 cells but not in MCF-7/ADR cells. Basal expression levels of Growth Arrest and DNA Damage 34 (GADD34), a regulator of $eIF2{\alpha}$, were higher in MCF-7/ADR cells compared to MCF-7 cells. Indeed, treatment with salubrinal, an inhibitor of GADD34, resulted in the upregulation of $eIF2{\alpha}$ phosphorylation and enhanced doxorubicin-mediated apoptosis in MCF-7/ADR cells. However, MCF-7 cells did not show such synergic effects. These results suggest that dephosphorylation of $eIF2{\alpha}$ by GADD34 plays an important role in doxorubicin resistance in MCF-7/ADR cells.

• Physical Therapy Rehabilitation Science
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• v.3 no.2
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• pp.107-111
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• 2014

Objective: In the present study, we investigated the protective effects of low-intensity treadmill training in doxorubicin-induced cardiotoxicity rat models. Design: Randomized controlled trial. Methods: In this study, we randomly divided them into four groups. The normal group included non-cardiotoxicity normal control (n=10), the control group included non-treadmill training after doxorubicin-induced cardiotoxicity (n=10), the experimental group I included low-intensity treadmill training (3 m/min) after doxorubicin-induced cardiotoxicity (n=10), and the experimental group II included low-intensity treadmill training (8 m/min) after doxorubicin-induced cardiotoxicity (n=10). Rats in the treadmill training group underwent treadmill training, which began at 2 weeks after first intraperitoneal injection. We determined the body weight change for each rat on days 1 and 21. Biochemical markers (lactate dehydrogenase [LDH], creatine kinase [CK], glutathion, aspartate transaminase [AST], and alanine transaminase [ALT]) concentration in the serum change of rats from all four groups was examined at the end of the experiment. Results: The results showed that the experimental group I and II showed a significant increase in body weight as compared with that of the control group (p<0.05). We observed that the biochemical markers (LDH, CK, glutathion, AST, and ALT) were improved in the experimental group I than the experimental group II (p<0.05). There was no difference between the experimental groups. Conclusions: In conclusion, our data suggest that low-intensity treadmill training applied after doxorubicin treatment protects against cardiotoxicity following treatment, possibly by enhancing antioxidant defenses and inhibiting cardiac muscle cell apoptosis.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.86-94
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• 2019

Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.389-397
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• 2020

Microglial cells function as major immune cells in the brain, playing an important role in the protection and damage of neurons. BV2 microglia, activated by drug stimulation, secrete inflammatory cytokines by activating the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway and are involved in neuroinflammatory and immune responses. The overactivation of microglia by stimuli can cause neuronal damage, leading to brain disease. Noni, a natural product, reduces the activity of microglia to prevent neuronal damage and is a potential natural medicine because it exerts excellent regeneration and anti-inflammatory effects on damaged cells. In this study, when noni was used to treat BV2 cells stimulated by the anti-cancer drug doxorubicin, it reduced the release of pro-inflammatory cytokines from BV2. On the other hand, neuronal damage is a side effect of doxorubicin. Therefore, the cytokines released from doxorubicin-stimulated BV2 cells treated with noni had a positive effect on the neuronal viability compared to those released from doxorubicin-stimulated BV2 cells not treated with Noni. Thus, Noni increases neuronal viability. These results suggest that noni inhibits the release of cytokines by regulating the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of BV2, thereby inhibiting neuronal damage.

• Journal of Microbiology and Biotechnology
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• v.24 no.9
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• pp.1238-1244
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• 2014

Dephosphocoenzyme A (CoaE) catalyzes the last step in the biosynthesis of the cofactor coenzyme A. In this study, we report the identification and application of CoaE from Stretomyces peucetius ATCC27952. After expression of coaE, the protein was found to have a molecular mass of 28.6 kDa. Purification of the His-tagged fused CoaE protein was done by immobilized metal-affinity chromatography, and then in vitro enzymatic coupling assay was performed. The increasing NADH consumption with time shed light on the phosphorylating activity of CoaE. Furthermore, the overexpression of coaA and coaE independently under the $ermE^*$ promoter in the doxorubicin -producing wild type strain, resulted in 1.4- and 1.5-fold enhancements in doxorubicin production, respectively. In addition, the overexpression of both genes together showed a 2.1-fold increase in doxorubicin production. These results established a positive role for secondary metabolite production from Streptomyces peucetius.

• Journal of Microbiology and Biotechnology
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• v.2 no.3
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• pp.153-160
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• 1992

The doxorubicin resistance locus from Streptomyces peucetius subsp. caesius (the doxorubicin producer, ATCC 27952) has been cloned. The sequence data over 4.4 kb regions reveals the presence of four possible open reading frames (ORFs). ORF2 and ORF3 would encode proteins containing 329 and 283 amino acids, respectively. The protein encoded by ORF2 has two almost identical ATP binding domains with p-glycoprotein, the product of a multidrug resistance gene from tumor cells, and that encoded by ORF3 has several hydrophobic domains suggesting that it is located in the bacterial membrane. These two remarkable similarities of the gene product to p-glycoprotein of mammalian tumor cells suggest that the two proteins may enable bacteria to extrude a variety of toxic agents, including daunorubicin and doxorubicin, by an ATP dependent efflux mechanism analogous to the multidurg resistance protein of cancer cells.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.167.2-168
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• 2003

Anticancer drug resistance occasionally occurs in malignant hematologic diseases such as acute myelocytic leukemia (AML) treated with chemotherapy and is a major problem to complete remission. Malignant cells primarily induce intrinsic resistance to treatment of anticancer drug, but gradually obtain acquired resistance to cytotoxic activities of chemotherapy. In this study, we monitored the expression profiles of doxorubicin resistance-related genes in AML-2/DX100, a doxorubicin-resistant human acute myelocytic leukemia cell line. (omitted)