• Journal of Ginseng Research
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• v.44 no.2
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.778-782
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• 2007

The Diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes, particularly NADPH oxidase. In this study, we investigated the effect of DPI on the cell growth progression of human colon cancer cells HCT-116 (wild-type p53), HT-29 (p53 mutant) and human breast cancer cells MCF-7 (wild-type p53). DPI treatment in cancer cells evoked a dose- and time-dependent growth inhibition, and also induced the cell cycle arrest in C2/M phase. The peak of cell population arrested in C2/M phase was observed at12 hr after treatment of DPI. In addition, DPI significantly induced the expression of p53, which induces proapoptotic genes in response to DNA damage or irreparable cell cycle arrest, at 6 hr in DPI-stimulated cells. However, a catechol apocynin, which inhibits the assembly of NADPH oxidase, did not induce p53 expression. This suggest that p53 expression induced by DPI is not associated with the inhibition of NADPH oxidase. In conclusion, we suggest that DPI induces the expression of wild-type p53 by ROS-in-dependent mechanism in several cancer cells, and upregulated p53 may be involved in regulatory mechanisms for growth inhibition and cell cycle arrest at C2/M phase in DPI-stimulated cells.

• Journal of Life Science
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• v.25 no.4
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• pp.406-415
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• 2015

In this study, we investigated the antioxidant activities and compared other physiological properties including anti-cancer and antimicrobial effects of several traditional Korean herb-combined remedies such as Gilgyung-tang (GGT), Daihwangmokdan-tang (DHMDT), Sagan-tang (SGT), Socheonryongtang (SCRT), Sihocheonggan-tang (SHCGT), Sipyukmiyuki-eum (SYMYKE) and Hwangheuk-san (HHS), which were recorded in “Dong-eui-bo-gam” for “Ongjeo”. Total phenolic contents of the herb medicines were in a rich order of GGT ＜ SYMYKE ＜ SCRT ＜ SHCGT ＜ DHMDT ＜ SGT ＜ HHS. Among them, HHS appeared highest in superoxide dismutase-like activity, ferric reducing antioxidant power, scavenging of 2,2’-diphenyl-1-picrylhydrazyl, and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical activity. Interestingly, there was a positive relationship between their total phenolic contents and their antioxidant activities. Although all of them showed anti-proliferative activities in human colon cancer HCT-116 cells, HHS was seven times higher than GGT. Antimicrobial activities against Escherichia coli and Helicobacter pylori were revealed only on SGT, SCRT, SYMYKE and HHS. Taken together, these findings reveal the potential use of traditional Korean herbal formulas as functional ingredients in antioxidant and physiological materials.

• Journal of Life Science
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• v.25 no.4
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• pp.450-455
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• 2015

This study compared the heavy metal contents and the effects of extracts from domestic and imported red sea bream on the antioxidant activity and cytotoxicity of human cancer cell lines. The antioxidant activity was measured using the fluorescently sensitive dye, 2’-7’ dichlorofluorescein-diacetate (DCFH-DA), and antiproliferative activity against AGS human gastric adenocarcinoma and HT-29 human colon cancer cell lines, which was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Domestic red sea bream had a higher mercury content when compared to imported red sea bream, but there was no significant difference in the lead content. Treatments with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from domestic and imported red sea bream dose-dependently decreased the H₂O₂ induced ROS production, compared to the control. The cell viability showed that treatments with the A+M and MeOH extracts had cytotoxicity in the growth of AGS and HT-29 cancer cells. In the case of AGS, the extracts from the domestic red sea bream were higher in inhibiting cancer cell growth, compared to imported red sea bream. Our results demonstrate that the heavy metal contents of domestic and imported red sea bream were below the limit of the Food Code of Korea. The results of the biological activities indicate that the antioxidant activity of extracts from imported red sea bream was more effective, while the extracts from the domestic red sea bream were stronger in cytotoxic activity.

• Journal of Life Science
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• v.17 no.10
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• pp.1368-1373
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• 2007

Inhibitory effects of several solvent fractions from soybean on mutagenicity using Salmonella typhimurium TA 100 in Ames test and growth of human cancer cells (AGS gastric adenocarcinoma, Hep 3B hepatocellular cancinoma and HT-29 colon cancer cells) were studied. The treatment of dichloromethane and ethylacetate fractions (2.5 mg/assay) extracted from soybean to Ames test system inhibited aflatoxin $B_1\;(AFB_1)$ induced mutagenicity by 83%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N#-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 67%) among solvent extracts, although the inhibitory effect was not stronger compared with $AFB_1$ induced mutagenicity. In sulforhodamine B (SRB) assay, the treatment of ethylacetate fraction (2 mg/assay) significantly inhibited the growth of AGS, Hep 3B and HT-29 cancer cells by 66%, 73% and 77%, respectively, followed with the intermediate and dichloromethane fractions. These results indicated that soybean fraction extracted with ethylacetate had higher inhibitory effects on $AFB_1$ and MNNG in Ames test and growth inhibition activity to human cancer cells was appeared, suggesting that soybean fraction extracted with ethylacetate may contain the biologically active compounds.

• Journal of Life Science
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• v.17 no.11
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• pp.1533-1538
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• 2007

This study was carried out to determine the inhibitory effects of solvent extracts from Sargassum hemiphyllum on growth of cancer cell lines (AGS human gastric adenocarcinoma and HT-29 human colon cancer cells) and production of lipid peroxides. Inhibitory effects of acetone with methylene chloride extract from S. hemiphyllum on the growth of AGS and HT-29 cancer cells were increased as dose dependent patterns (p<0.05). The methanol extract was more effective on inhibition of growth of AGS. The treatments of hexane, 85% aq. methanol, butanol and water fractions significantly inhibited the growth of cancer cells (p<0.05) and the inhibitory effect was stronger in HT-29. In DCFH-DA (dichlorodihydrofluorescin diacetate) assay, acetone with methylene chloride and methanol extracts showed a stronger inhibitory effect on the production of cellular lipid peroxides (p<0.05) compared with the butanol and hexane fractions. These results indicate that the consumption of S. hemiphyllum may be recommended as a potent functional food for preventing cellular oxidation and cancer.

• Journal of Life Science
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• v.22 no.9
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• pp.1145-1151
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• 2012

Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.

• Journal of Life Science
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• v.20 no.5
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• pp.639-643
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• 2010

Sudden deaths have occurred in feedlot cattle with marked necro-hemorrhagic enteritis of the jejunum, ileum and colon. Suckling beef calves are the most frequently affected. Over-consumption of large amounts of milk, inadequate colostrum intake, chilling and stress are conducive to the development of enterotoxemia. Enterotoxemia caused by Clostridium perfringens type D mostly occurs following a sudden change of diet, particularly to feeds made richer in order to grow the cattle to market weight in feedlots. During July 2006, sudden deaths of cattle occurred in the Youngcheon regional area of Gyeongbuk province. There were no significant clinical signs except anorexia, depression, intermittent diarrhea and mild respiratory failure. Histological findings revealed a prominent intranuclear inclusion as well as infiltration of the globular leukocytes in various organs including the heart, kidneys, liver, spleen and lymph nodes. Spleen and lymphatic tissues showed lymphatic necrosis and a starry sky appearance. In the submucosa of the small intestines, basophilic aggregation was detected with massive infiltration of the globular leukocytes and eosinophils. Gram staining for the tissue sections containing inclusions of the small intestines revealed a positive histochemical reaction. Taken together, we suggest that Clostridium perfringens type D-induced enterotoxemia is determined to be the cause of sudden death of feedlot cattle.

• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.115-118
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• 2010

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.