• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1119-1125
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• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1126-1133
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• 2002

Conjugated linoleic acid (CLA) is a collective term for a class of positional and geometric conjugated dienoic isomers of linoleic acid (LA) and has anti-cancer activity in experimental animals. We have previously observed that an isomeric mixture of CLA and trans-10,cis-12 (t10c12) inhibited cell growth in a dose-dependent manner whereas LA and cis-9,trans-11 (c9t11) had no effect. The present study examined whether the CLA mixture and t10c12 induce apoptotic cell death. TSU-Prl cells were incubated for three days in serum-free medium in the absence or presence of individual fatty acids, and the DNA fragmentation assay was performed. Cells treated with the CLA mixture or t10c12 produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. By contrast, LA and c9t11 had no effect. Western immunoblot analysis of total lysates revealed that t10c12 reduced anti-apoptotic, 26 kDa, Bcl-2 protein levels by 49$\pm$8% compared with controls, whereas this CLA isomer did not alter pro-apoptotic,21 kDa, Bax protein levels. These results suggest that growth inhibitory effect of the t10c12 CLA isomer may, at least in part, be attributed to Increased apoptotic death in TSU-Prl cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.911-917
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• 2016

Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.907-913
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.428-436
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• 2003

Epidemiological studies have observed a negative association between increased consumption of green and yellow vegetables and cancer incidence. These vegetables contain carotenoids, which are reported to exhibit anticarcinogenic effects. Overexpression of ErbB2 and ErbB3 genes is a frequent event in several human cancers. The present study was performed to determine whether $\alpha$-carotene, $\beta$-carotene, lutein, or lycopene inhibits cell growth and to assess such an effect is related to changes in the levels of the ErbB receptor family and tile ErbB3 receptor signaling pathway in HT-29 cells. HT-29 cells were cultured in serum-free medium in the presence of various concentrations (0~100 $\mu$M) of the individual carotenoids. $\alpha$ -Carotene and lycopene significantly inhibited cell growth in a dose-dependent manner, whereas lutein slightly inhibited cell growth and $\beta$-carotene increased cell growth. Lycopene is more potent than $\alpha$ -carotene in inhibiting HT-29 cell growth. Lycopene inhibited DNA synthesis and induced apoptosis of HT-29 cells. The ErbB3 ligand heregulin (HRG) increased cell growth but did not prevent the lycopene-induced inhibition of cell growth. Lycopene decreased ErbB2 protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that lycopene inhibited HRG-induced phosphorylation of ErbB3, recruitment of the 985 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to the ErbB3 receptor, and phosphorylation of Akt. These results indicate that downregulation of ErbB2/ErbB3/PI3K/Akt signaling may be one of the mechanisms by which lycopene inhibits HT-29 cell pro-liferation and induces apoptosis.

• Journal of Life Science
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• v.30 no.4
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• pp.402-409
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• 2020

Nervous necrosis virus (NNV) contains a bi-segmented viral genome, RNA1 (3.4 kb, RdRp), and RNA2 (1.4 kb, capsid protein) in a small particle (25 nm). Despite its extremely compact size, NNV has caused serious damage by infecting approximately 120 fish species worldwide since it was first reported in the late 1980s. In order to minimize the damage caused by NNV infection and develop effective vaccines, it is necessary to understand the intra cellular signaling system according to NNV infection. NNV infection induces cell cycle arrest at the G1 phase via the p53-dependent pathway to use the cellular system for its replication. Otherwise, host cells recognize NNV infection through the RIG-1-like receptor (RLR) signaling pathway to control the virus and infected cells, and then ISGs required for antiviral action are activated via the IFN signaling pathway. Moreover, apoptosis of infected cells is triggered by the unfolded protein response (UPR) through ER stress and mitochondria-mediated cell death. Cell signaling studies on the NNV infection mechanisms are still at an early stage and many pathways have yet to be identified. Understanding the various disease-specific cellular signaling systems associated with NNV infection is essential for rapid and accurate diagnosis and vaccine development.

• Journal of Life Science
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• v.22 no.8
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• pp.1018-1023
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• 2012

Snail is a zinc finger transcription factor that induces epithelial-to-mesenchymal transition (EMT), which promotes tumor invasion and metastasis by repressing E-cadherin expression. In addition, Snail restricts the cellular apoptotic response to apoptotic stimuli or survival factor withdrawal; however, its molecular mechanism remains largely unknown. In this study, we have investigated the mechanism underlying Snail-mediated chemoresistance to 5-fluorouracil (5-FU), one of the most widely used anti-cancer drugs. When Snail was overexpressed by doxycycline (DOX) in MCF-7 #5 cells, it inhibited 5-FU-induced apoptotic cell death and switched the cell death mode to necrosis. Snail expression, either by DOX treatment in MCF-7 #5 cells or by the transfection of Snail expression vectors pCR3.1-Snail-Flg, phosphorylation-resistant pCR3.1-S104, and 107A Snail-Flg in MCF-7 cells specifically induced PTEN down-regulation/inactivation and Akt/PKB activation, without affecting ERK1/2 activity. In addition, Snail prominently suppressed 5-FU-induced increases in p53 levels. These findings demonstrate that Snail switches 5-FU-induced apoptosis to necrosis through the activation of Akt/PKB and the down-regulation of p53 levels.

• Korean Journal of Food Science and Technology
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• v.36 no.6
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• pp.1001-1007
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• 2004

Chloroform layer from methanol extract of Corni fructus (Cornaceae) showed strong antiproliferation effect on human cancer cell lines by SRB assay. Anticarcinogenic-active compound was isolated and purified by silica gel column and thin layer chromatograpies, and identified as ursolic acid ($3{\beta}$-hydroxyrus-12-ene-28-oic acid, MW:456) by mass and IR spectrophotometries, and $^1H-and\;^{13}C-NMRs$. The compound inhibited proliferation of A549 (human lung cancer cell line) and MCF-7 (human breast cancer cell line) cells in dose-dependant manner when treated for 48 hr. Inhibition rates of both cells were over 40% and 90% compared with control cells at the $30\;{\mu}g/mL\;and\;100\;{\mu}g/mL$, respectively. Morphology of cells treated with the compound for 15 hr at $10\;{\mu}g/mL$ was distorted with shrinked cell mass, and cell number was lower than that of control cells. Cell cycle analysis showed sub-G1 phase arrest in both cell lines following 15 hr exposure to the compound; % of cell phase increased to 11.7 and 11.2% compared to the control of 4.0% and 2.1% in A549 and MCP-7 cells, respectively.

• Korean Journal of Food Science and Technology
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• v.36 no.6
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• pp.968-973
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• 2004

Effects of Erythronium japonicum methanol extract on ICR mouse with induced abdominal cancer and L1210 cells were studied. Administration of methanol extract ($10-100\;{\mu}g/20\;g$ body weight) prolonged life by 47.8% and decreased number of L1210 cells with $IC_{50}\;of\;54.6\;{\mu}g/mL$ after 3 days culture, whereas little effect was observed against normal lymphocytes (<6% compared to 83.2% of L1210 cells under the same condition). Increased SOD and GPx enzyme activities, and remarkably augmented generation of ${O_2}^-$ ion in L1210 cells by E. japonicum extract, implied that reactive oxygen species including ${O_2}^-$ ion, might have participated in L1210 cell death

• Applied Biological Chemistry
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• v.49 no.4
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• pp.270-275
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• 2006

[ $2{\beta},\;3{\alpha}$ ], 23-trihydroxyrus-12-ene-28-oic acid was isolated from Trapa pseudoincisa S. et Z. It has a common structure of pentacyclic triterpenes and belongs to the amyrin ursolic acid group. The cytotoxic effect of this compound was investigated in human hepatoma cell line HepG2. $2{\beta},\;3{\alpha}$, 23-trihydroxyrus-12-ene-28-oic acid showed dose-dependent cytotoxicity in HepG2 cells. Confocal microscopy data showed that green fluorescence was increased in $2{\beta},\;3{\alpha}$, 23-trihydroxyrus-12-ene-28-oic acid treated-HepG2 cells in a time-dependent manner. $2{\beta},\;3{\alpha}$, 23-trihydroxyrus-12-ene-28-oic acid also increased the sub-G1 cell population of HepG2 cells as well as ladder-like DNA fragmentation. Taken together, our results indicate that $2{\beta},\;3{\alpha}$, 23-trihydroxyrus-12-ene-28-oic acid induced apoptosis in HepG2 cells.