• IMMUNE NETWORK
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• v.23 no.2
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• pp.16.1-16.19
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• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

• Journal of Life Science
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• v.28 no.10
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• pp.1201-1211
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• 2018

The study compared the anti-aging, anti-adipogenesis, and anti-tumor effects of epigallocatechin-3- gallate (EGCG) in various cancer cell lines (SNU-601, MKN74, AGS, MCF-7, U87-MG, and A-549) and normal cell lines (MRC-5 fibroblasts, dental tissue-derived mesenchymal stem cells [DSC], and 3T3-L1 pro-adipocytes). Half inhibitory concentration ($IC_{50}$) values were significantly (p<0.05) higher in normal cell lines (~50 uM), when compared to that in cancer cell lines (~10 uM). For anti-aging effects, MRC-5 and DSC were exposed to 10 uM EGCG for up to five passages that did not display any growth arrest. Population doubling time and senescence-related ${\beta}-galactosidase$ ($SA-{\beta}-gal$) activity in treated cells were similar to untreated cells. For anti-adipogenic effects, mouse 3T3-L1 pre-adipocytes were induced to adipocytes in an adipogenic differentiation medium containing 10 uM EGCG, but adipogenesis in 3T3-L1 cells was not inhibited by EGCG treatment. For anti-tumor effects, the cancer cell lines were treated with 10 uM EGCG. PDT was significantly (p<0.05) increased in EGCG-treated SNU-601, AGS, MCF-7, and U87-MG cancer cell lines, except in MKN74 and A-549. The level of telomerase activity and cell migration capacity were significantly (p<0.05) reduced, while $SA-{\beta}-gal$ activity was highly up-regulated in EGCG treated-cancer cell lines, when compared to that in untreated cancer cell lines. Our results have demonstrated that EGCG treatment induces anti-tumor effects more efficiently as noted by decreased cell proliferation, cell migration, telomerase activity, and increased $SA-{\beta}-gal$ activity than inducing anti-aging and anti-adipogenesis. Therefore, EGCG at a specific concentration can be considered for a potential anti-tumor drug.

• Journal of Life Science
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• v.26 no.7
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• pp.835-846
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• 2016

Chemo-resistance is the biggest issue of effective cancer therapy. ABCG2 is highly correlated with multi-drug resistance, and represent a typical phenotype of multiple cancer stem-like cells. Accumulating evidence recently reported that oncolytic viruses represent a new strategy for multiple aggressive cancers and drug resistant cancers including cancer stem cell-like cells and ABCG2 expressing cells. In this study, we generated an evolutionally engineered vaccinia virus, SLJ-496, for drug-resistant cancer therapy. We first showed that SLJ-496 treatment enhanced tumor affinity using cytopathic effect assay, plaque assay, as well as cell viability assay. Next, we clearly demonstrated that in vitro SLJ-496 treatment represents significant cytotoxic effect in multiple cancers including colorectal cancer cells (HT-29, HCT-116, HCT-8), gastric cancer cells (AGS, NCI-N87, MKN-28), Hepatocellular carcinoma cells (SNU-449, SNU-423, SNU-475, HepG2), as well as mesothelioma cell (NCI-H226, NCI-H28, MSTO-221h). Highly ABCG2 expressing HT-29 cells represent cancer stem like phenotype including stem cell marker expression, and self-renewal bioactivities. Interestingly, we demonstrated that in vitro treatment of SLJ-496 showed significant cytotoxicity effect, as well as viral replication capacity in ABCG2 overexpressing cell. In addition, we also demonstrated the cytotoxic effect of SLJ-496 in Adriamycin-resistant cell lines, SNU-620 and ADR-300. Taken together, these findings provide us a pivotal clue that cancer therapy using SLJ-496 vaccinia virus might be new therapeutic strategy to overcome ABCG2 expressing cancer stem-like cell and multiple chemo-resistance cancer cells.

• Food Science and Preservation
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• v.20 no.6
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• pp.854-862
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• 2013

We examined the quality characteristics and functionalities of Korean and Japanese spring Baechu cabbages and the kimchi prepared with them. To study the physiochemical properties of the cabbages and the kimchis, we measured their water content, pH, acidity, microbial counts, and springiness. On the third week of the kimchi fermentation at $5^{\circ}C$, their sensory properties and in vitro DPPH radical scavenging and anticancer activities using AGS human gastric cancer cells were determined. The Japanese Baechu contained 97.1% water, and the Korean Baechu, 92.4%. The comparison of the textures of the raw Baechu and the brined Baechu showed that the Korean Baechu had higher springiness scores than the Japanese Baechu. After four-week fermentation, the springiness score of the kimchi with Korean Baechu was 53.5%, significantly higher than the 41.4% of the kimchi with Japanese Baechu. The kimchi prepared with Korean Baechu had a low total bacterial count but higher Lactobacillus sp. and Leuconostoc sp. counts than the kimchi with Japanese Baechu. The kimchi prepared with Korean Baechu had the highest overall acceptability score in the sensory evaluation test. The DPPH radical scavenging activity of the kimchi with Korean Baechu was 83.2%, and that of the kimchi with Japanese Baechu, 46.1%. When the AGS human gastric cancer cells were treated with the kimchis, the kimchi prepared with Korean Baechu showed a 45% cancer cell growth inhibition rate, and the kimchi with Japanese Baechu, 26%, at 1 mg/mL of methanol extracts. At the 2 mg/mL concentration, the kimchis with Korean Baechu and Japanese Baechu showed 97% and 74% inhibition, respectively. The Korean Baechu showed better quality than the Japanese Baechu, and the kimchi prepared with the Korean Baechu showed better kimchi quality and functionality than the Japanese Baechu.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.1
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• pp.25-31
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• 2009

This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

• Applied Biological Chemistry
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• v.49 no.4
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• pp.322-327
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• 2006

Food constituents analysis of Acer tegmentosum. Maxim.(Acer TM) stem was carried out according to AOAC method, and the antiradical activity on DPPH and cytotoxicity on human cell lines (AGS, HepG2, A549, MCF-7 and Chang) for the 80% ethylalcohol(EtOH) extracts of Acer TM stem were studied. The antiradical activity on DPPH radical of the ethylacetate(EtOAc) fraction of the bark showed a higher activity than that of $\alpha$-tocopherol, ascorbic acid and BHT. The inhibition activity of the 80% EtOH extracts from Acer TM stem on human cancer cell lines by SRB assay indicated a dose-dependent growth inhibition on most human carcinoma cells. The growth inhibition rate of each human cancer cell line showed 91.3% to AGS, 75.0% to A549, 74.1% to HepG2, and 70.2% to MCF-7 cells, respectively, when the 80% EtOH extract(1 mg/ml) of Acer TM stem was added.

• Food Science and Preservation
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• v.24 no.2
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• pp.289-293
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• 2017

Ethanol extract of garlic peels (GPE) was investigated for its antiproliferative effects on human cancer cell lines. Human lung cancer cell line A549 treated with $500{\mu}g/mL$ GPE resulted in the growth inhibition of A549 by 90%. In stomach cancer cell AGS proliferation inhibition activity, GPE showed 45% and 71% inhibition of AGS growth at $1,000{\mu}g/mL$ and $2,000{\mu}g/mL$, respectively. GPE inhibited the growth of the breast cancer cells MCF-7 effectively at low concentration and showed 78% and 90% inhibitions of MCF-7 growth at $200{\mu}g/mL$ and $500{\mu}g/mL$, respectively. GPE showed very significant antiproliferation effect on liver cancer cell line Hep3B and inhibited Hep3B cell growth by 57% at $100{\mu}g/mL$, and the inhibition's rate increased up to 87% at $500{\mu}g/mL$. Antiproliferation effect of GPE on colorectal cancer cell HT-29 showed 15% reduction of HT-29 cell growth at $200{\mu}g/mL$ and the growth rate was reduced in a dose dependent manner up to $1,000{\mu}g/mL$. These results indicated that GPE had high antiproliferation effects on breast and liver cancer cell lines at low concentrations ($200{\mu}g/mL$), and by higher concentrations over $500{\mu}g/mL$, GPE inhibited the growth of A549 and HT-29. The results of our study suggested the potential use of garlic peels for use as an excellent antiproliferative substance for human cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1589-1594
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• 2016

Piperine [(E,E)-5-(3,4-methtylenedioxyphenyl)-2,4-pentadienolypiperidide] is a principal of Piperaceae, including Piper nigrum L. and Piper longum Linn., which has been used as a spice and traditional medicine. In this study, we investigated whether or not piperine has anti-cancer effects on AGS human gastric cancer cells. The results demonstrated that piperine not only inhibited proliferation using MTT assay but also induced apoptotic bodies using DAPI assay in a dose-dependent manner in response to piperine. Expression levels of p53, Bax (pro-apoptotic), cleaved caspase-9, and cleaved-PARP increased, whereas expression levels of Bcl-2, XIAP (anti-apoptotic), and Akt decreased in a dose-dependent manner compared with the control by western blotting analysis. To identify the connection between phospo-Akt and Bcl-2 family in response to piperine, LY249002 (Akt inhibitor) was treated with piperine ($150{\mu}M$). The results were shown that expression of phospo-Akt was reduced whereas expression of Bax and cleaved-PARP increased in a dose-dependent manner. These results indicate that piperine induced apoptosis in AGS cells and may serve as a chemopreventive or therapeutic agent for human gastric cancer.

• Microbiology and Biotechnology Letters
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• v.36 no.2
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• pp.106-114
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• 2008

One bacterium, which showed strong antagonistic activity against H. pylori KCCM 41756, was isolated from kimchi. The strain NO1 was designated as Lactobacillus plantarum NO1 based on Gram staining, biochemical properties, and 16S rRNA gene sequencing. The culture medium $(2{\sim}4{\mu}g/ml)$ of Lb. plantarum NO1 reduced $(40{\sim}60%)$ the urease activity of H. pylori KCCM 41756. Lb. plantarum NO1 inhibited the binding of H. pylori to human gastric cancer cell line, AGS cells, by more than 33%. Lb. plantarum NO1 exhibited high viability (maintained initial viable cell count of $10^9CFU/ml$) in 0.05 M sodium phosphate buffer (pH 3.0) for 2 h, in artificial gastricjuice for 2 h and in 0.3%, 0.5% oxgall for 24 h. Hemolysis phenomena did not observed when Lb. plantarum NO1 was incubated in the blood agar media. We concluded that Lb. plantarum NO1 can be a good candidate as a probiotic, harboring anti-H. pylori activity.

• 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.