• Title/Summary/Keyword: in vitro cancer research

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Trends in the development of human stem cell-based non-animal drug testing models

  • Lee, Su-Jin;Lee, Hyang-Ae
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.6
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    • pp.441-452
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    • 2020
  • In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

Antioxidant Activity and in vitro for Anticancer Effects of Manufactured Fermented Mulberry Leaf Tea (뽕잎발효차 제조에 따른 항산화 및 in vitro 항암활성)

  • Bae, Man-Jong;Ye, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.6
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    • pp.796-804
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    • 2010
  • This study was conducted to compare and analyze the qualitative property of MLT (mulberry leaf tea) and FMLT (fermented mulberry leaf tea) based on the antioxidant, anticancer activities of various extracts. When the antioxidant activity of MLT and FMLT extracts was evaluated, the electron donating activity was found to increase proportionally as the concentration of each extract increased. In addition, the extract of FMLT showed a higher electron donating activity than that of MLT. Furthermore, the ethanol extracts showed the highest electron donating ability. When the SOD activity was evaluated, it was also found to increase proportionally with the concentration of each extract. Furthermore, the SOD activity of the ethanol extract group was the highest, whereas the SOD like activities of both MLT and FMLT were similar. When nitrite decomposition was evaluated for each pH, the highest value was observed at pH 1.2. Finally, the nitrite deleting ability was the highest for the ethanol extracts. When each extract of MLT and FMLT was analyzed in vitro for anticancer effects, they were found to decrease the number of cancer cells proportionally as the concentration of extract increased for both HeLa cells and MCF-7 cells. Furthermore, FMLT was found to exert a greater inhibition of cancer cells than MLT. Among the extract groups, the ethanol extract induced the greatest inhibition of the development of cancer cells, and these effects were greater against MCF-7 cells than HeLa cells.

Upregulation of Mir-34a in AGS Gastric Cancer Cells by a PLGA-PEG-PLGA Chrysin Nano Formulation

  • Mohammadian, Farideh;Abhari, Alireza;Dariushnejad, Hassan;Zarghami, Faraz;Nikanfar, Alireza;Pilehvar-Soltanahmadi, Yones;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8259-8263
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    • 2016
  • Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and $42.3{\mu}M$ and 58.2, 44.2, $36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer.

Inhibitory Effect of Low-molecularized Polymannuronate on Proliferation and DNA Synthesis of Human Colon Cancer Cells (저분자 polymannuronate의 인체 대장암세포 증식 및 DNA 합성 저해 효과)

  • Kim In-Hye;Nam Taek-Jeong
    • Journal of Life Science
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    • v.15 no.6 s.73
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    • pp.857-862
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    • 2005
  • This study investigated the proliferation and DNA synthesis inhibitory effect of concentrations ($0.01\%$, $0.1\%$, $0.25\%$, $0.5\%$) when added whole molecular-, 40 kDa-, or 10 kDa polymannuronate on human colon cancer cells, HT-29, DLD-1, and WiDr, in vitro. In order to determine the proliferation inhibitory effect of low-molecularized polymannuronate, the treatment of whole molecular-, 40 kDa-, 10 kDa-, polymannuronate ($0.25\%$) to the HT-29 cancer cells inhibited proliferation of cancer cells by $41\%$, $69.1\%$, and $75.6\%$, respectively. DLD-1 cancer cell was not relation of molecular weight and concentration. WiDr cancer cell depend on concentration without molecular weight. In addition, whole molecular-, 40 kDa-, 10 kDa poly mannuronate ($0.25\%$) significantly inhibited DNA synthesis of HT-29 cancer .cells by $78\%$, $58\%$, and $56\%$, respectively. And morphological changes not found under microscope by polymannuronate. Therefore polymannuronate would be helpful to colon cancer treatment as well as cancer prevention and this study would be the basic source for further research of polymannuronate.

Phytochemical Constituents of Nelumbo nucifera

  • Kim, Ki-Hyun;Chang, Sang-Wook;Ryu, Shi-Yong;Choi, Sang-Un;Lee, Kang-Ro
    • Natural Product Sciences
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    • v.15 no.2
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    • pp.90-95
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    • 2009
  • Phytochemical investigation of the MeOH extract of the leaves of Nelumbo nucifera resulted in the isolation of five norsesquiterpenes, four flavonoids, two triterpenes and one alkaloid. Their chemical structures were characterized by spectroscopic methods to be (E)-3-hydroxymegastigm-7-en-9-one (1), (3S,5R,6S,7E)- megastigma-7-ene-3,5,6,9-tetrol (2), dendranthemoside B (3), icariside $B_2$ (4), sedumoside $F_1$ (5), luteolin (6), quercetin 3-0-${\beta}$-D-glucuronide (7), quercetin 3-0-${\beta}$-D-glucoside (8), isorhamnetin 3-0-rutinoside (9), alphitolic acid (10), maslinic acid (11), and N-methylasimilobine (12). Norsesquiterpenoids (1-5) and triterpenes (10-11) were isolated for the first time from this plant. Compounds 6 and 10-12 exhibited considerable cytotoxicity against four human cancer cell lines in vitro using a SRB bioassay.

Cytotoxicity of Paecilomyces tenuipes Against Human Carcinoma Cells, HepG2 and MCF-7 In Vitro

  • Shim, Joong-Sup;Chang, Hae-Ryong;Min, Eung-Gi;Kim, Yong-Hae;Han, Yeong-Hwan
    • Mycobiology
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    • v.29 no.3
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    • pp.170-172
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    • 2001
  • The methanolic extract of fruiting body of Paecilomyces tenuipes DGUM 32001 showed significant cytotoxicity against human cancer cells: HepG2 and MCF-7. The methanolic extract was further fractionated with organic solvents such as chloroform and ethyl acetate in that order. Among the fractions tested, the ethyl acetate fraction showed the highest cytotoxicity against the carcinoma tested. The $IC_{50}$ values of ethyl acetate fraction against HepG and MCF-7 were 40 and 9.6 ${\mu}g/ml$, respectively.

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Study on the antimicrobial activities of herbal extracts against Helicobacter pylori (Helicobacter pylori에 대한 항균활성을 가진 천연물의 검색과 항균력 비교 연구)

  • Lee, Hyun-A;Kim, Okjin
    • Korean Journal of Veterinary Research
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    • v.53 no.2
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    • pp.117-123
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    • 2013
  • Infection with Helicobacter (H.) pylori is strongly associated with duodenal and gastric ulcers. Substantial epidemiological data has revealed that high rates of H. pylori infection might be related to high rates of gastric cancer. In this study, a medicinal herbal extracts were examined and screened for anti-H. pylori activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity study, the inhibitory zone tests with 74 herbal compounds were conducted. As the results, thirteen compounds including Cinnamomi Cortex, Magnoliae Cortex and Meliae Fructus were revealed strong anti-H. pylori activities.

Synthesis and Antitumor Activity of 3-Arylisoquinoline Derivatives

  • Cho, Won-Jea;Yoo, Su-Jeong;Park, Myun-Ji;Chung, Byung-Ho;Lee, Chong-Ock
    • Archives of Pharmacal Research
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    • v.20 no.3
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    • pp.264-268
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    • 1997
  • In order to study the structure-activity relationship of 7, 8-dimethoxy-2-methyl-3-(4, 5-methylenedioxy-2-vinylphenyl)isoquinoline-1(2H) -one (2), which has exhibited significant antitumor activity, chemical modifications of 2 were performed to yield the corresponding products (3-7). Further systematic uses of an efficient procedure for the synthesis of 3-arylisoquinoline derivatives produced the substituted compounds (9a-9g), which were tested for in vitro antitumor activity against five different human cancer cell lines.

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Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy

  • Narayan Bashyal;Young Jun Lee;Jin-Hwa Jung;Min Gyeong Kim;Kwang-Wook Lee;Woo Sup Hwang;Sung-Soo Kim;Da-Young Chang;Haeyoung, Suh-Kim
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.438-447
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    • 2023
  • Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

In-vitro Anticancer and Antioxidant Activity of Gold Nanoparticles Conjugate with Tabernaemontana divaricata flower SMs Against MCF -7 Breast Cancer Cells

  • Preetam Raj, J.P;Purushothaman, M;Ameer, Khusro;Panicker, Shirly George
    • Korean Chemical Engineering Research
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    • v.54 no.1
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    • pp.75-80
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    • 2016
  • Biologically stabilized gold nanoparticles were synthesized from the flower aqueous extract of T. divaricata. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, Zeta sizer, FTIR and TEM analysis. T. divaricata reduced gold nanoparticles having particle size and potential of 106.532 nm and -10.2 mV, respectively, with a characteristic peak of 550 nm in UV-visible spectrophotometer. FTIR graph after comparison between the crude flower extract and gold nanoparticles showed three major shifts in the functional groups. The morphology and size of the gold nanoparticles were examined by HRTEM analysis, which showed that most of the nanoparticles were nearly spherical with size of 100 nm. The gold nanoparticles synthesized demonstrated potent anticancer activity against MCF-7 cell line. The findings conclude that the antioxidant molecule present in T. divaricata may be responsible for both reduction and capping of gold nanoparticles which possess potential applications in medicine and pharmaceutical fields.