• 대한의생명과학회지
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• 제25권4호
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• pp.293-301
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• 2019

Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제67권3호
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• pp.212-220
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• 2009

Background: Ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii has been increasing and growing as a threat in intensive care units. Limited therapeutic options have forced clinicians to choose colistin with or without combination of other antibiotics. We tried to compare the effectiveness between colistin monotherapy and combination therapy based on in vitro synergistic tests. Methods: From January 2006 to December 2007 in medical ICU of a tertiary care hospital in Korea, We reviewed the medical records of patients treated with intravenous colistin due to ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. Results: A total of 41 patients were analyzed. 22 patients had been treated with colistin monotherapy and 19 patients with colistin and combination antibiotics that were found to have in vitro synergistic effects. Baseline characteristics were similar in both groups but the mean duration of colistin administration was significantly longer in the combination group (19.1${\pm}$11.2 days vs. 12.3${\pm}$6.8 days, p=0.042). There were no significant differences in outcome variables between the two groups. Conclusion: Combination treatment based on the in vitro antimicrobial synergy test did not show better outcomes compared with colistin monotherapy in VAP caused by multi-drug resistant A. baumannii.

• 대한미생물학회지
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• 제21권2호
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• pp.271-276
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• 1986

Amphotericin B and rifampin or 5-fluorocytosine were tested for synergism against Candida albicans in a synthetic mdium. The test was based on viability studies in which fungicidal activity was determined during the incubation hours of drug exposure. Concentration of amphotericin B(0.2ug per ml and 0.4ug per ml) in combination with inactive concentration of rifampin(12.5ug per ml) or 5-fluorocytosine(25ug per ml) resulted in rapid decrease of colony froming unit(CFU). On the basis of these and earlier studies, it is concluded that amphotericin Band rifampin or 5-fluorocytosine are synergistic against various yeasts and yeast-like fungi under widely differing experimental conditions.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.59-66
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• 1997

This study was done to determine that vitamins I and C are synergistic in protecting liver cells during hepatic ischemia and repefusion. Rats treated with vitamins I and C were subjected to 60 min of hepatic ischemia and to 1 and 5 hr of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by vitamins E, C or its combination. Hepatic wet weight-to-dry weight ratio was increased in ischemic group, but this increase was prevented by combination of vitamin I and C. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and vitamin C alone and combination of vitamin I and C restored their secretion. Cytochrome P-450 content and aminopyrine N-demethylase activity were decreased by ischemia/ reperfusion and restored by vitamin C and combination of vitamin I and C to the level of sham-operated rat. Aniline p-hydroxylase activity was increased by ischemia/reperfusion and this increase was prevented by vitamin E. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory and microsomal functions by increasing lipid peroxidation and vitamins I and C synergistically ameliorates these changes.

• 생약학회지
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• 제30권1호
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• pp.40-47
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural hesperetin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Hesperetin inhibited plaque formations of HSV-1 and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-2 with selectivity index (SI) of 9.8 than on HSV-1 with SI of 8.4. The combined antiherpetic effects of hesperetin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of hesperetin with acyclovir on HSV-1 and HSV-2 showed synergistic effects with CI values of $0.29{\sim}0.73$ for 50%, 70%, 90% effective levels and those with vidarabine showed partially synergistic or additive effects with CI values of $0.83{\sim}1.33$.

• Fisheries and Aquatic Sciences
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• 제26권2호
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• pp.133-144
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• 2023

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC₅₀) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

• 대한약침학회지
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• 제25권2호
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• pp.79-87
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• 2022

Since ancient times, plants have been a major source of novel drug molecules and have been used in the treatment of different infectious diseases. Secondary plant metabolites have miraculous healing properties and show potent therapeutic responses when used in combination drug therapy. The prime objective of this review is to summarize the concept of drug combination with special emphasis on the synergistic interactions between plant-derived bioactive phytochemicals with commercially available antimicrobial agents. The study also assesses the roles, importance, and applicability of phytochemicals in the management of different diseases. The review focuses on different aspects of combined antimicrobial activities, the possible mechanisms involved, and the current status of research in the field. The study was conducted based on an extensive literature survey that resulted in the following hypothesis: secondary metabolites derived from plants possess remarkable therapeutic activities. The study was designed as a systematic review that ensures unbiased and accurate representations of the relevant data and information. Jadad scale selection criteria were used for qualitative analysis of the articles to assess them based on the relevant secure score (minimum and maximum scores range between 1 and 5, respectively). Articles with secure scores > 3 were considered for the study. A comprehensive literature survey was conducted using resource databases including PubMed, Google Scholar, Bielefeld Academic Search Engine, Research Gate, Scopus, Medline, and Science Direct up to June 2019. This article contains concise information about the most commonly used bioactive phytochemicals with potent antifungal and antibacterial effects.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.139-150
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• 2017

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

• Natural Product Sciences
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• 제17권2호
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• pp.160-164
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• 2011

The purpose of this investigation was to extract the bioactive agents from Alpinia officinarum Hance. The methanol with ethylacetate extracts alone and combined were examined for their activities against VRE (vancomycin-resistant enterococci) and pathogenic yeast in vitro. The incidence of infections caused by VRE and other pathogenic microorganisms and the importance of using novel synergistic drug combinations has become important. Previously, we reported the antimicrobial effects of the butanol extract from Lonicera japonica and have evaluated combinations of solvent extracts, with a focus on the MeOH and EtOAc extracts from A. officinarum. In the present study, enhanced inhibitory effects were achieved by employing a combination of the two solvent extracts. The MeOH and EtOAc combination was especially effective against four VRE strains: E. faecalis (K-10-22), E. faecaium (K-11-212), E. faecalis (K-10-57) and E. faecalis (K-10-361) with MIC values of 12.5, 12.5, 6.25 and 25 ${\mu}g/ml$, respectively. Thus, the combination was more effective than other antibiotics such as kanamycin, gentamicin or tetracycline against bacteria including E. coli, Staphylococcus aureus, and Micrococcus luteus. In addition, the combination was effective against yeasts such as Candida albicans, Candida tropicalis and Cryptococcus neoformans.

• Interdisciplinary Bio Central
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• 제5권2호
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• pp.3.1-3.7
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• 2013

Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.