• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• Korean Journal of Plant Resources
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• v.28 no.5
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• pp.561-567
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• 2015

This study aims to evaluate the antitumor effect of Adonis multiflora, one of the plants in the Ranunculaceae, on mice to which hepatoma cells were transplanted and to suggest its possibility as a candidate natural substance to replace antitumor drugs. We performed the MTT assay to assess the extract had a decrease in the growth rate of hepatoma cells depending on concentration. In particular, 100 ㎍/㎖ of the extract showed 40% of growth retardation rate. We assessed the autophagy activity to identify the inhibitory autophagy mechanism of tumor cells in the extract. This proved that the activity increases more as the concentration of the extract is higher. We conducted the Western blot test to confirmed the expression of two proteins LC3 and p62. The expression of p62 was in inverse proportion to the concentration of the extract whereas LC3-Ⅱ increased more as the concentration of the extract was higher. This showed that an increase in the autophagy relies on the conentration of the extract. We performed a test to discover the influence of the extracts on hepatoma cells transplanted to mice. The test proved that the extract triggers a significant decrease in the growth rate of tumor cells. Compared to the start of the test, the size of tumor cells with 50, 100 and 200 ㎎/㎏ of the extract respectively increased by 4, 3.7 and 3.5 times whereas in the controlling group by 6.3 times. The size of tumor cells in benign tumor controlling group increased by 3.1 times. This showed a significant decrease in the growth rate of tumor cells compared to the controlling group. We carried out the experiment of influence of the extract on the expression of two proteins LC3 and p62 in the tumor tissue transplanted into mice. The experiment showed that LC3-II increases more as the concentration of the extract is higher. However, there was a rapid decrease in p62 with 200 ㎎/㎏ of the extract compared to the controlling group. In this study, we proved that the autophagy activity of Adonis multiflora extract inhibits the growth of hepatoma cells by in vitro and in vivo experiments. In conclusion, the inhibitory autophagy mechanism of tumor cells in the extract can be used as a new treatment of antitumor.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.704-716
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• 2020

Background: Ginsenoside Rh2 (GRh2) is a characterized component in red ginseng widely used in Korea and China. GRh2 exhibits a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, and anticancer properties. However, its effects on Toxoplasma gondii (T. gondii) infection have not been clarified yet. Methods: The effect of GRh2 against T. gondii was assessed under in vitro and in vivo experiments. The BV2 cells were infected with tachyzoites of T. gondii RH strain, and the effects of GRh2 were evaluated by MTT assay, morphological observations, immunofluorescence staining, a trypan blue exclusion assay, reverse transcription PCR, and Western blot analyses. The in vivo experiment was conducted with BALB/c mice inoculated with lethal amounts of tachyzoites with or without GRh2 treatment. Results and conclusion: The GRh2 treatment significantly inhibited the proliferation of T. gondii under in vitro and in vivo studies. Furthermore, GRh2 blocked the activation of microglia and specifically decreased the release of inflammatory mediators in response to T. gondii infection through TLR4/NF-κB signaling pathway. In mice, GRh2 conferred modest protection from a lethal dose of T. gondii. After the treatment, the proliferation of tachyzoites in the peritoneal cavity of infected mice markedly decreased. Moreover, GRh2 also significantly decreased the T. gondii burden in mouse brain tissues. These findings indicate that GRh2 exhibits an antieT. gondii effect and inhibits the microglial activation through TLR4/NF-κB signaling pathway, providing the basic pharmacological basis for the development of new drugs to treat toxoplasmic encephalitis.

• Journal of Digital Convergence
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• v.13 no.5
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• pp.337-344
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• 2015

Medicinal plants containing wellness-fusion-complex compound are increasingly being pursued as suitable alternative sources of various biological properties. In this study, inhibitory effect of Quintinia acutifolia, which is a New Zealand plant, on P388 murine lymphocytic leukemia cells using MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide] assay. Based on $^1H-NMR$, $^{13}C-NMR$ spectral data and other spectral analysis, 2,3,2'',3''-tetrahydroochanaflavone (1) and 2'',3''-dihydroochana-flavone (3) inhibited the leukemia cells were purified from the plants. 2,3,2'',3''-tetrahydroochanaflavone (1) and 2'',3''-dihydroochana-flavone (3) are biflavonoids possessing two basic flavonoids and actively inhibited growth of P388 murine lymphocytic leukemia cells with a 50% inhibitory concentration ($IC_{50}$) of $8.2{\mu}g/mL$ and $3.1{\mu}g/mL$, respectively. Specially, 2'',3''-dihydroochana-flavone (3) possessed unconjugated flavonone system, which isn't consist of a pair with B ring of 2,3,2'',3''-tetrahydroochanaflavone (1). Therefore, the two compounds could be considered as a candidate for development of anticancer drugs and need to much studies in the future.

• Korean Journal of Medicinal Crop Science
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• v.24 no.2
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• pp.121-128
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• 2016

Background: Turmeric (Curcuma longa L.) that is used as a food material has antioxidant, anticancer and anti-inflammatory properties. Recently the demand for functional foods and drugs has increased. The present study was carried out to determined of contents of residual sulfur dioxide, heavy metals, ash, acid insoluble ash and curcuminoids in turmeric from the Seoul Yak-ryeong market. Methods and Results: A total of 31 samples were obtained. Residual sulfur dioxide was not detected in any samples. Heavy metals (arsenic, cadmium, lead and mercury) were analyzed by ICP-MS (Inductively Coupled Plasma Mass Spectrometer) and a mercury analyzer and were detected in the ranges of 0.00 - 0.28, 0.00 - 0.07, 0.00 - 0.29 and 0.002 - 0.027mg/g respectively. No significant difference were observed between the average heavy metal contents of domestic and imported tumeric. However, average content of ash in domestic samples (7.8%) were significantly higher than that in imported samples (6.1%), whereas that of curcuminoids was significantly higher in imported samples (47.6mg/g) than in domestic samples (11.2mg/g). The average content of acid insoluble ash was not significantly different between two sample types (0.9% in each). Conclusions: There are no specific standards for turmeric used as food materials. Therefore, this study can be provided as basic data for the establishment of quality standards for turmeric.

• Journal of Society of Preventive Korean Medicine
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• v.13 no.2
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• pp.51-64
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• 2009

Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.228-235
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• 2021

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods: The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps. Results: The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK-OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

• Journal of Life Science
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• v.31 no.12
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• pp.1128-1141
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• 2021

'Angelica' is one of the most traditionally consumed medicinal herbs around Northeast Asia including Korea for treatments of various diseases or health care purposes like hematopoiesis, blood circulation for women, sedative, analgesic, and a tonic medicine etc. Angelica gigas Nakai, a Korean native species of Angelica, is clearly different from the others in containing a high concentration of active ingredients like pyranocoumarines including decursin, decursinol, and decursinol angelate. These compounds have various kinds of positive effects such as anti-tumor activity including the precaution of neutropenia occurred during anticancer drug administration, improvements of metabolic disorders, menstrual irregularity, impairment of renal function, respiration improvement, cognition-enhancement, anti-inflammatory effect, anti-oxidative effect, enhancing fertility and so forth. Thus it implies incredible potentialities in future development for foods and drugs. However, certain purity-related qualities and/or overdose in food products can cause side effects like toxicities; therefore, their safety profiles should also be considered. This review focuses on the positive and negative effects of three pyranocoumarines in Angelica gigas Nakai and some possibilities and considerations for future food and drug products development.

• Journal of Life Science
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• v.33 no.8
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• pp.663-679
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• 2023

This review analyzes research trends related to new drug development using artificial intelligence from 2010 to 2022. This analysis organized the abstracts of 2,421 studies into a corpus, and words with high frequency and high connection centrality were extracted through preprocessing. The analysis revealed a similar word frequency trend between 2010 and 2019 to that between 2020 and 2022. In terms of the research method, many studies using machine learning were conducted from 2010 to 2020, and since 2021, research using deep learning has been increasing. Through these studies, we investigated the trends in research on artificial intelligence utilization by field and the strengths, problems, and challenges of related research. We found that since 2021, the application of artificial intelligence has been expanding, such as research using artificial intelligence for drug rearrangement, using computers to develop anticancer drugs, and applying artificial intelligence to clinical trials. This article briefly presents the prospects of new drug development research using artificial intelligence. If the reliability and safety of bio and medical data are ensured, and the development of the above artificial intelligence technology continues, it is judged that the direction of new drug development using artificial intelligence will proceed to personalized medicine and precision medicine, so we encourage efforts in that field.

• Journal of Life Science
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• v.33 no.7
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• pp.593-604
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• 2023

The ocean accounts for over 70% of the Earth's surface and is a space of largely unexplored unknowns and opportunities. Korea is a peninsula surrounded by the sea on three sides, emphasizing the importance of marine research. The ocean has an extremely complex environment with immense biological diversity. In terms of microbiology, the marine environment has varying factors like extreme temperature, pressure, solar radiation, salt concentration, and pH, providing ecologically unique habitats. Due to this variety, marine organisms have very different phylogenetic classifications compared with terrestrial organisms. Although various microorganisms inhabit the ocean, studies on the diversity, isolation, and cultivation of marine microorganisms and the secondary metabolites they produce are still insufficient. Research on bioactive substances from marine microorganisms, which were rarely studied until the 1990s, has accelerated in terms of natural products from marine Actinomycetes since the 2000s. Since then, industries for bioplastic and biofuel production, carbon dioxide capture, probiotics, and pharmaceutical discovery and development of antibacterial, anticancer, antioxidant, and anti-inflammatory drugs using bacteria, archaea, and algae have significantly grown. In this review, we introduce current research findings and the latest trends in life science and biotechnology using marine microorganisms. Through this article, we hope to create consumer awareness of the importance of basic and applied research in various natural product-related discovery fields other than conventional pharmaceutical drug discovery. The article aims to suggest pathways that may boost research on the optimization and application of future marine-derived materials.