• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.511-518
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• 2001

The effect of mycolactone, a recently reported apoptosis-inducing factor, was investigated in SCC15 oral squamous cell carcinoma(OSCC) cell line. Mycolactone rapidly induced cell death in OSCC cells in 2days, which was similar to that found in apoptotic cell such as detaching from culture plate and rounding-up of cells. Apoptotic cells were increased 4hrs after mycolactone treatment and more than half of cells showed apoptosis after 72hrs. Caspase 3 activation a biochemical evidence of apoptosis, was determined by Western blotting. Caspase 3 activation was started at 2hrs that lasted until 8hrs after mycolactone treatment. The expression of bcl-2 family genes was determined to explain the mechanism of apoptosis found in OSCC cells. The expressions of bad, bak, and bax (pro-apoptotic genes) and bcl-w and bcl-2 genes (anti-apoptotic genes) were not changed by mycolactone treatment. The expression of bcl-xi was decreased 8 hrs after mycolactone treatment. Mcl-1 expression was initially increased at 2 hrs which was decreased 8 hrs after mycolactone treatment. The down-regulation of these two anti-apoptotic genes might explain the mycolactone-induced apoptosis in OSCC cells. In this study, mycholactone was revealed to induce cell death in OSCC cells apoptosis and the apoptosis mechanism of OSCC cells was shown to be down-regulation of anti-apoptotic genes, bcl-xi and mcl-1. These results suggested the applicability of mycolactone for the development of an anti-cancer drug candidate by inducing apoptosis of OSCC cancer cell.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2335-2341
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• 2014

Chemical investigation on the methanol extract of the starfish Ctenodiscus crispatus resulted in the isolation of five steroids, (22E,$24{\zeta}$)-26,27-bisnor-24-methyl-$5{\alpha}$-cholest-22-en-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,25-pentol 25-O-sulfate (1), (22E,24R,25R)-24-methyl-$5{\alpha}$-cholest-22-en-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,25,26-hexol 26-O-sulfate (2), (28R)-24-ethyl-$5{\alpha}$-cholesta-$3{\beta}$,5,$6{\beta}$,8,$15{\alpha}$,28,29-heptaol-24-sulfate (3), (25S)-$5{\alpha}$-cholestane-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,$16{\beta}$,26-hexaol (4), and ${\Delta}7$-sitosterol (5). Their structures were identified by extensive spectroscopic analyses, including 1D, 2D NMR and MS and chemical methods. Compound 4 showed cytotoxicity against human hepatoma HepG2 and glioblastoma U87MG cells via inhibition of cell growth and induction of apoptosis. Induction of apoptosis by 4 was demonstrated by cell death, DNA fragmentation, increased Bax/Bcl-2 protein ratio and the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP).

• Korean Journal of Veterinary Research
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• v.49 no.1
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• pp.1-8
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• 2009

The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.619-624
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• 2011

Tea extract (TE) has been shown to have anti-tumor properties in a wide variety of experimental systems. We evaluated green tea extract (GTE) as a biochemical modulator for the antitumor activity of cisplatin and doxorubicin in the treatment of human lung cancer A549 cells. Cells were grown in RPMI-1640 medium supplemented with 10% (v/v) heat-inactivated fetal bovine serum and two antibiotics (100 units/mL penicillin and $100\;{\mu}g$/mL streptomycin). Two types of TE, epigallocatechin galate (EGCG) and GTE, were used in this experiment. The cells were seeded at $1{\times}10^4$ cells/well in the RPMI-1640 media with or without TE ($100\;{\mu}g$/mL) and then treated with different concentrations of doxorubicin ($0{\sim}14\;{\mu}g$/mL) or cisplatin ($0{\sim}35\;{\mu}g$/mL). After incubation in 5% $CO_2$ at $37^{\circ}C$ for 24 hr, cell viability was determined with a MTT assay. We used a Western blot to detect the influence of EGCG and GTE on the expression of p53 and caspase-3 genes in the A549 cells. A549 cell viability decreased to 15% with a $10\;{\mu}g$/mL concentration of cisplatin, and to 21% with a $8\;{\mu}g$/mL concentration of doxorubicin, as measured with the MTT assay. However, pre-treatment of the cells with EGCG ($100\;{\mu}g$/mL) or GTE ($100\;{\mu}g$/mL) resulted in decreased cell viability with $6\;{\mu}g$/mL of cisplatin and $4\;{\mu}g$/mL of doxorubicin. There was no apparent change in cell viability between EGCG or GTE administration in cisplatin- or doxorubicin-induced cytotoxicity in A549 cells. The levels of p53 and caspase-3 in the A549 cells increased with both EGCG and GTE treatment. We found that GTE could potentially affect cisplatin- or doxorubicin-induced cytotoxicity of A549 cells, which may be useful in the chemotreatment of cancer.

• Environmental Mutagens and Carcinogens
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• v.24 no.3
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• pp.113-120
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• 2004

Chromium compounds are known human and animal carcinogens. In this study, the effects of sodium chromate on apoptosis and cell cycle were investigated in order to unveil the elements of early cellular responses to the metal. Using Chinese hamster ovary cells(CHO-K1-BH4), we found taht chromium (VI) treatment induced apoptosis in these cells, as signified by nuclear fragmentation, DNA laddering on agarose gel electrophoresis, and an increased proportionof cells with hypodiploid DNA. Preceding these changes, chromium (VI) treatment increased caspase 3 pritease activity and also increased expression of p53 protein, while the level of bcl2 protein was not changed. Coincubation with caspase inhibitor, Z-DEVD-FMK, inhibited chromium-induced apoptosis. In the flow cytometric analysis using propidium iodide fluorescence, an increase of cell population in G2/M phase was shown in cells exposed to at least 160 $\mu\textrm{m}$ of sodium chromate for 72h, form 9.8% for 0$\mu\textrm{m}$ chromium (VI) to 26.4% for 320$\mu\textrm{m}$ chromium(VI). Taken together, these findings suggest that chromium(VI)-induced apoptosis is accompanied by G2/M cell cycle arrest, and that p53-mediated pathway may be involved in positive regulation of G2/M arrest and a concurred apoptosis in CHO cells.

• BMB Reports
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• v.45 no.9
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• pp.496-508
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• 2012

Fas-associated protein with death domain (FADD), an adaptor that bridges death receptor signaling to the caspase cascade, is indispensible for the induction of extrinsic apoptotic cell death. Interest in the non-apoptotic function of FADD has greatly increased due to evidence that FADD-deficient mice or dominant-negative FADD transgenic mice result in embryonic lethality and an immune defect without showing apoptotic features. Numerous studies have suggested that FADD regulates cell cycle progression, proliferation, and autophagy, affecting these phenomena. Recently, programmed necrosis, also called necroptosis, was shown to be a key mechanism that induces embryonic lethality and an immune defect. Supporting these findings, FADD was shown to be involved in various necroptosis models. In this review, we summarize the mechanism of extrinsic apoptosis and necroptosis, and discuss the in vivo and in vitro roles of FADD in necroptosis induced by various stimuli.

• Natural Product Sciences
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• v.19 no.2
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• pp.127-136
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• 2013

Ionizing radiation, including that evoked by gamma (${\gamma}$)-rays, induces oxidative stress through the generation of reactive oxygen species, resulting in apoptosis, or programmed cell death. This study aimed to elucidate the radioprotective effects of hyperoside (quercetin-3-O-galactoside) against ${\gamma}$-ray radiation-induced apoptosis in Chinese hamster lung fibroblasts, V79-4 and demonstrated that the compound reduced levels of intracellular reactive oxygen species in ${\gamma}$-ray-irradiated cells. Hyperoside also protected irradiated cells against DNA damage (evidenced by pronounced DNA tails and elevated phospho-histone H2AX and 8-oxoguanine content) and membrane lipid peroxidation. Furthermore, hyperoside prevented the ${\gamma}$-ray-provoked reduction in cell viability via the inhibition of apoptosis through the increased levels of Bcl-2, the decreased levels of Bax and cytosolic cytochrome c, and the decrease of the active caspase 9 and caspase 3 expression. Taken together, these results suggest that hyperoside defend cells against ${\gamma}$-ray radiation-induced apoptosis by inhibiting oxidative stress.

• BMB Reports
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• v.49 no.3
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• pp.159-166
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• 2016

Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.253-259
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• 2016

Previously, we found that KTH-13 isolated from the butanol fraction of Cordyceps bassiana (Cb-BF) displayed anti-cancer activity. To improve its antiproliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl- 2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10495-10500
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• 2015

Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.