• 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 Applied Biological Chemistry
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• v.57 no.1
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• pp.41-45
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• 2014

In the present study, red ginseng extracts were fermented by Paecilomyces tenuipes and the protopanaxdiol-type ginsenosides in the extracts were bio-transformed to F2, Rg3, Rg5, Rk1, Rh2, and CK determined by a high-pressure liquid chromatography analysis. It indicates that P. tenuipes is a microorganism to biotransform protopanaxdiol-type ginsenosides to their less glucosidic metabolites. Other biotransformed metabolites during fermentation were also analyzed using a GC-MS and identified as 2-methyl-benzaldehyde, 4-vinyl-2-methylphenol, palmitic acid, and linoleic acid. Antiulcerogenic activity of the fermented red ginseng extract (FRGE) on gastric mucosal damage induced by 0.15 M HCl in ethanol in rats was evaluated. FRGE was shown to have a potent protective effect on gastritis with 60.5% of inhibition rate at the dose of 40 mg/kg when compared to 54.5% of the inhibition rate at the same dose for stillen, the currently used medicine for treating gastritis. Linoleic acid showed a strong inhibition on gastritis with 79.3% of inhibition rate at the dose of 40.0 mg/kg. FRGE exhibited a distinct anticancer activity including growth inhibition of the two human colon cancer cells HT29 and HCT116. HT29 cells were less susceptible to FRGE in comparison with HCT116 cells. Taken together, fungal fermentation of the red ginseng extract induced hydrolysis of some ginsenosides and FRGE exhibited potent antiulcerogenic and anticancer activities. These results refer to use FRGE as a new source for treating human diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3975-3978
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• 2013

Background: Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies to combat these pathologies seems to be the use of protease inhibitors. LC-pi I, II, III and IV (Lavatera cashmerian-protease inhibitors) have been found in vitro to strongly inhibit trypsin, chymotrypsin and elastase, proteases contributing to tumour invasion and metastasis, indicated possible anticancer effects. The purpose of this study was to check in vitro anticancer activity of these four inhibitors on human lung cancer cell lines. Material and Methods: In order to assess whether these inhibitors induced in vitro cytoxicity, SRB assay was conducted with THP-1 (leukemia), NCIH322 (lung) and Colo205, HCT-116 (colon) lines. Results: LC-pi I significantly inhibited the cell proliferation of all cells tested and also LC-pi II was active in all except HCT-116. Inhibition of cell growth by LC-pi III and IV was negligible. $IC_{50}$ values of LC-pi I and II for NCIH322, were less compared to other cell lines suggesting that lung cancer cells are more inhibited. Conclusion: These investigations might point to future preventive as well as curative solutions using plant protease inhibitors for various cancers, especially in the lung, hence warranting their further investigation.

• Journal of Microbiology and Biotechnology
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• v.26 no.8
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• pp.1490-1503
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• 2016

Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT-116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.49.1-49.1
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• 2008

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.3
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• pp.325-330
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• 2010

This study was conducted to investigate the effects of 70% ethanol extracts of various germinated-rough rice cultivars: ('Ilpum', 'Goami2', 'Keunnun', 'Sulgaeng', 'Baegjinju', and 'Heugkwang') on proliferation of human cancer cell lines (MKN-45, HCT116 and NCI-H460). Antiproliferation effects of rough rice on different cancer cell lines were higher in after germination than before germination. The viability of HCT-116 colon cancer cells was lowest at 18.89% in after germination of 'Heugkwang' at 1.0 mg/mL. The cell viability of MKN-45 lung cancer cells and MKN-45 stomach cancer cells were in the range of 5~10% in after germination of 'Ilpum', 'Goami2', 'Baegjinju', and 'Sulgaeng', and 'Heugkwang' at 1.0 mg/mL. These results suggest that germinated rough rice might have a potential preventive effect on human cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.1
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• pp.1-7
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• 2011

Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 112 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell. However, ROS-dependent activation of ERK1/2 and p38 MAPK, but not JNK, might not be involved in the curcumin-induced autophagy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.36-41
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• 2010

This study was conducted to investigate the effects of fermented ginseng extract by mushroom mycelia on antiproliferation of cancer cells. Phellinus linteus, Ganoderma lucidum, and Hericium erinaceum mycelia were inoculated to ginseng. The effects of fermented ginseng extract on antiproliferation of stomach (MKN-45), colon (HCT116), mammary (MCF-7), lung (NCIH460), prostate (PC-3), and liver (HepG2) cancer cells were investigated by MTT assay. Fermented ginseng extract showed significant antiproliferation effects compared with fresh ginseng extract. Fermented ginseng extract by P. linteus, G. lucidum, and H. erinaceum mycelia showed growth-inhibitory effect of 44.50, 17.75 and 43.98% viability at 1.5 mg/mL on the MKN-45 cell line, 62.86, 3.73, and 54.55% at 1.5 mg/mL on the HCT116 cell line, 41.81, 7.01, and 37.84% at 1.5 mg/mL on the MCF-7 cell line, 53.52, 5.31, and 35.27% at 1.5 mg/mL on the NCIH460 cell line, 35.05, 3.07, and 44.29% at 1.5 mg/mL on the PC-3 cell line, and 59.57, 6.34, and 4.97% at 1.5 mg/mL on the HepG2 cell line, respectively. These results indicated that fermented ginseng by G. lucidum mycelium showed the highest antiproliferation effect against various cancer cells.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1615-1623
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• 2021

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.356-361
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• 2012

Caffeine is a xanthine alkaloid derivative found in many foods and beverages. Dietary caffeine may interact with commonly-consumed over-the-counter (OTC) drugs in body. In this study, cytotoxic effects on the intestinal cells by combined treatment of caffeine with several OTC drugs, including ibuprofen, aspirin, and acetaminophen. Cytotoxic effect of caffeine was more potent in normal intestinal INT 407 cells than in colon cancer HCT 116 cells. Relative toxicity of caffeine and the OTC drugs was significantly enhanced in INT 407 cells when treated together. Intracellular thiol levels of the cells treated with the OTC drugs increased in the presence of caffeine. When HCT 116 cells were incubated with each OTC drug after or before caffeine treatment, the relative cytotoxicity of the OTC drugs increased. The present study may provide basic information about possible health effects through the interactions between caffeine and OTC drugs in the intestinal cells.