• Korean Journal of Food Science and Technology
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• v.44 no.4
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• pp.452-459
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• 2012

This study was conducted in order to investigate the effect of resveratrol on the induction of apoptosis in MDA-MB-231 breast cancer cells. The result of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl terazolium bromide (MTT) assay shows that cell viability significantly decreased in a dose and time-dependent manner. 4',6-diamidino-2-phenylindole (DAPI) staining shows significantly increased chromatin condensation in a dose and time-dependent manner. Resveratrol increased the expression of p53, cleaved-caspase-3, and cleaved-caspase-9, whereas the expression of PI3K/Akt decreased in a time-dependent manner. We investigated the in vivo tumor growth inhibitory effect of resveratrol. Tumor volume was significantly decreased in the 50 mg/kg resveratrol-administration group compared to the control group. In the 50 mg/kg treated group. Apoptosis cells were frequently observed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. Immunohistochemistry staining shows increased the expression of p53, cytochrome-C, and cleaved-caspase-3 in the 50 mg/kg treated group. These results indicate that resveratrol induced apoptosis through PI3K/Akt and p53 signal pathway in MDA-MB-231 cell.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1235-1242
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• 2006

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.6
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• pp.657-662
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• 2009

Antioxidant and anticancer activities of water and ethanol extracts of defatted soybean grits (DSG) fermented Bacillus subtilis NUC1 were determined and compared with those of the raw DSG. The fermented defatted soybean grits (FDSG) exhibited higher total polyphenols and flavonoids contents than DSG. The ethanol extracts of FDSG (FD-E) showed the highest polyphenol and flavonoid contents with 23.35 mg/g and 3.48 mg/g, respectively. Particularly, FD-E showed higher DPPH radical scavenging activities with $RC_{50}$ of 0.32 mg/mL than other samples with $RC_{50}$ of 1.10${\sim}$3.89 mg/mL. The water and ethanol extracts of FDSG and DSG showed growth inhibitory effects against AGS, A549 and Hela cancer cells in a dose-dependent manner, and especially FD-E showed the highest growth inhibition effects. FD-E induced apoptosis in Hela cells through an increased activation of caspase-3 and caspase-3 target protein, PARP, but rarely affected caspase-7.

• Applied Biological Chemistry
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• v.50 no.1
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• pp.63-67
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• 2007

The neuroprotective effect of methanolic extracts from Dendrobium nobile Lindl. (DME) against $H_{2}O_{2}$-induced neurotoxicity in PC12 cells was investigated. The treatment of PC12 cells with various DME concentrations under $H_{2}O_{2}$ resulted in the induction of protective effect in a dose-dependent manner, as determined by the results of an MTT reduction assay, an LDH release assays, and a morphological assay. Interestingly, we also detected reduction of apoptotic bodies and inhibition of caspase-3 activity by DME in $H_{2}O_{2}$-indeced PC12 cells. These data show that the neuroprotective effect of DME against PC12 cells might be related to the suppression of caspase-3 activation. Therefore, these results suggest that DME could be a new potential candidate as chemotherapeutic agents against neuronal diseases.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.298-306
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• 2004

Purpose: The purpose of this study was to identify Radiosensitivity of proteins in tissues with different radiosensitivity. Materials and Methods: C3H/HeJ mice were exposed to 10 Gy. The mice were sacrifiud 8 hrs after radiation. Their spleen and liver tissues were collected and analyzed histologicaly for apoptosis. The expressions of radiosusceptibillty protein were analyzed by 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Resilts: The Peak of apoptosis levels were $35.3{\pm}1.7{\%}$ in spleen and $0.6{\pm}0.2{\%}$ in liver at 8 hrs after radiation. Liver, radioresistant tissues, showed that the levels of ROS metabolism related to proteins such as cytochromm c, glutathione S transferase, NADH dehydrogenase, riken cDNA and peroxiredoxin Vl increased after radiation. The expression of cytochrome c increased significantly in spleen and liver tissues after radiation. In spleen, radiosensitivity tissue, the identified proteins showed a significantly quantitative alteration following radiation. It was categorized as signal transduction, apoptosis, cytokine, Ca signal related protein, stress-related protein, cytoskeletal regulation, ROS metabolism, and others. Conclusion: Differences of radiation-induced apoptosis by tissues specifted were coupled with the induction of related radiosensitivity and radioresistant proteins. The result suggests that apoptosis relate protein and redox proteins play important roles in this radiosusceptibility.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.2
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• pp.63-70
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• 2006

Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.1074-1077
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• 2004

The effect of gradient eluted fractions from Et$_2$O extracts of Polyporus umbellatus screlotium was investigated on the viability of leukemia cell lines, K-562, L-1210, HL-60 and U-937 cells. Among those fractions, fraction 2 showed mild cytotoxic effect on L-1210 and HL-60 cells. Fraction 3 showed cytotoxic effect on 4 cell lines, and cytotoxic effect was the most potent on L-1210. The hallmark of apoptosis, DNA fragmentation, also appeared by fraction 3 on L-1210 after 48 hr treatment. Furthermore, this fraction was shown to be able to induce cell death on L-1210 cells by the inhibition of DNA synthesis in [$^3$H]thymidine incorporation test. From these results, P. umbellatus involves a potent chemical component that inhibits the viability of leukemia cell lines, L-1210. Further studies about the components of fraction 3 to function as a apoptosis inducer are necessary.

• Korean Journal of Food Science and Technology
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• v.53 no.6
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• pp.756-760
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• 2021

Frankincense has been used as a traditional medicine for treating rheumatoid arthritis, dermatitis, and muscle pain. In this study, the anti-tuberculosis effects of Frankincense were evaluated in immune responses of macrophages. Frankincense methanol extract was not cytotoxic to the host. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay using human macrophage (THP-1) cells did not show cytotoxic effects or morphological changes with treatments of 31.3, 62.5, and 125 ㎍/mL Frankincense methanol extract (FRM). Inhibitory effects of Frankincense methanol extract on the growth of Mycobacterium tuberculosis in human macrophages were investigated. The immune response was measured by monitoring the levels of TNF-α and IL-1β in THP-1 cells with or without M. tuberculosis infection under Frankincense methanol extract treatment. Inflammatory cytokine levels and M. tuberculosis numbers were reduced in THP-1 cells treated with Frankincense methanol extract. Therefore, Frankincense methanol extract could be used as a potential anti-tuberculosis agent.

• Journal of Life Science
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• v.31 no.10
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• pp.954-959
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• 2021

Apoptosis is an important mechanism that regulates cellular populations to maintain homeostasis, and the caspases, a family of cysteine proteases, are key mediators of the apoptosis pathway. Caspase-8 is an initiator caspase of the extrinsic apoptotic pathway, which is initiated by extracellular stimuli. Caspase-8 have two conserved domains, N-terminal tandem death effector domains (DED) and C-terminal two catalytic domain, which are important for this extrinsic apoptosis pathway. In extrinsic apoptosis pathway, death receptors which members of TNF superfamily are activated by binding of death receptor specific ligands from cell outside. After the activated death receptors recruit adaptor protein Fas-associated death domain protein (FADD), death domains (DD) of death receptor and FADD bind to each other and FADD combined with death receptor recruits procaspase-8, a precursor form of caspase-8. The DED of FADD and procaspase-8 bind to one another and FADD-bound procaspase-8 is activated by cleavage of the prodomain. This death receptor-FADD-caspase-8 complex called death inducing signaling complex (DISC). Cellular FLICE-inhibitory proteins (c-FLIPs) regulate caspase-8 activation by acting both anti- and pro-apoptotically, and caspase-8 activation initiates the activation of executioner caspases such as caspase-3. Finally activated executioner caspases complete the apoptosis by acting critically DNA degradation, nuclear condensation, plasma membrane blebbing, and the proteolysis of certain caspase substrates.

• Journal of Life Science
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• v.31 no.10
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• pp.873-884
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• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.