• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1584-1592
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• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is traditional medicinal plant generally used in Oriental medicine therapy. We previously reported that the water extract of H. cordata inhibited cell proliferation and induced apoptosis in human breast carcinoma cells. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of H. cordata (MEHC) in human lung carcinoma A549 cells. It was found that MEHC could inhibit the cell growth in a dose-dependent manner, which was associated with morphological change and apoptotic cell death as determined by formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase cells. Apoptosis of A549 cells by MEHC was also connected with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. MEHC treatment induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of poly(ADP-ribose) polymerase (PARP), ${\beta}$-catenin and phospholipase (PLC)-${\gamma}$1 protein expression. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.696-700
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• 2009

Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.

• Journal of Life Science
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• v.26 no.10
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• pp.1130-1136
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• 2016

The purpose of this study was to investigate the anti-proliferative and apoptotic effects of acid extract of Gracilaria verrucosa (AEG) on RC-58T/h/SA#4 primary human prostate cancer cells. AEG significantly decreased the cell viability of prostate cancer cells in a dose-dependent manner. AEG also showed relatively low cytotoxicity on normal cell (RWPE-1). The morphology of prostate cancer cells treated with AEG was distorted to shrunken cell masses. In addition, it was revealed that AEG induced cell death as evidenced by increased formation of apoptotic body and nuclear condensation. Furthermore, AEG clearly modulated the down regulation of Bcl-2 (anti-apoptotic)/Bax (pro-apoptotic) family and activated caspase-3 as an effector caspase in a dose-dependent manner. AEG inhibited cell proliferation induced by environmental hormones as a bisphenol A in a dose-dependent manner. These results indicate that AEG act as anti-proliferative effects as a potential therapeutic agent on primary human prostate cancer cells.

• Journal of Food Hygiene and Safety
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• v.27 no.4
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• pp.406-414
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• 2012

This study was designed to investigate the effect of fucoidan on the activation of macrophage and on induction of apoptosis in AGS cell. To measure the activity of macrophages, NO and TNF-${\alpha}$ assays were performed in Raw 264.7 cell. Treatment with fucoidan significantly increased production of NO and TNF-${\alpha}$, indicating activation of macrophages. The result of MTT assay shows that cell viability was significantly decreased in a dose and time-dependent manner. Fucoidan increased to enhance mitochondrial membrane permeability, as well as the cytochrome c release from the mitochondria. Fucoidan decreased Bcl-2 and XIAP expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 were increased, and the inactivation of Akt was decreased in a time-dependent manner. Caspase inhibitor, z-VAD-FMK, canceled the apoptosis of fucoidan, expression of Bax and caspase-9 were decrease. These results indicate that fucoidan induces activation of macrophage and apoptosis through activation of caspase on AGS cell.

• Toxicological Research
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• v.16 no.2
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• pp.133-139
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• 2000

This study was designed to evaluate the mechanism by which reactive nitrogen intermediates (RNI) induced the cytotoxicity of human doparminergic neuroblastoma SH-SY5Y cells. 3-Morpholino-sydnonimine (SIN-l), a donor of peroxynitrite (ONOO) and sodium nitroprusside (SNP), a donor of nitric oxide (NO) induced cell detachment and apoptotic death, as characterized by chromatin condensation, the ladder pattern fragmentation of genomic DNA and morphological nuclear changes. SIN-l also induced the activation of caspase 3-like protease in a time-dependent manner. Exogenous antioxidants, such as reduced glutathione (GSH), N-acetylcysteine (NAC), and selenium protected the cells from apoptotic death and reduced the activation of caspase 3-like protease by SIN-1. Furthermore, SIN-l directly reduced the intracellular levels of glutathione. Taken together, these data suggested that RNI including NO and peroxynitrite decrease the concentration of intracellular antioxidant such as GSH, which lead to the apoptotic death of human neuroblastoma SH-SY5Y cells.

• Toxicological Research
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• v.29 no.4
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• pp.257-261
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• 2013

${\alpha}$-Curcumene is one of the physiologically active components of Curcuma zedoaria, which is believed to perform anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the mechanism of the apoptotic effect of ${\alpha}$-curcumene on the growth of human overian cancer, SiHa cells. Upon treatment with ${\alpha}$-curcumene, cell viability of SiHa cells was inhibited > 73% for 48 h incubation. ${\alpha}$-Curcumene treatment showed a characteristic nucleosomal DNA fragmentation pattern and the percentage of sub-diploid cells was increased in a concentration-dependent manner, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of ${\alpha}$-curcumene, which mediates cell death. These results suggest that the apoptotic effect of ${\alpha}$-curcumene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.363-368
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• 2006

EGCG [(-)-epigallocatechin-3-gallate], a major component of green tea has been considered as a major antioxidant constituent. In addition to having been considered for cancer treatment as a chemopreventive and chemotherapeutic agent, EGCG has recently been attributed an anti-proliferative effect. We re-examined the latter finding in this study and added specific focus on the ability of EGCG to induce apoptosis in human osteogenic sarcoma (HOS) cells. Antiproliferative action of EGCG $(IC_{50}=35.3{\pm}6.0{\mu}g/mL)$ appeared to be linked to apoptotic cell death based on morphological changes, chromosomal DNA degradation, and an increase in the $sub-G_1$ apoptotic cell population. Treatment of HOS cells with EGCG gradually activated caspase-3, an established inducer of apoptotic cell death.

• Korean Journal of Clinical Laboratory Science
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• v.42 no.1
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• pp.46-54
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• 2010

Ceramide induces cell death in a variety of cell types however, the underlying molecular mechanisms related to renal epithelial cells remain unclear. The present study was undertaken to determine the role of extracellular signal-regulated protein kinase (ERK) in ceramide-induced cell death in renal epithelial cells. An established renal proximal tubular cell line of opossum kidney (OK) cells was used for this research. Ceramide induced apoptotic cell death in these cells. Western blot analysis showed that ceramide induced activation of ERK. The ERK activation and cell death induced by ceramide were prevented by the ERK inhibitor PD98059. Ceramide caused cytochrome C release from mitochondria into the cytosol as well as activation of caspase-3. Both effects were prevented by PD98059. The ceramide-induced cell death was also prevented by a caspase inhibitor. These results suggest that ceramide induces cell death through an ERK-dependent mitochondrial apoptotic pathway in OK cells.

• Biomedical Science Letters
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• v.29 no.3
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• pp.201-205
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• 2023

Free adenine is mainly made during the polyamine synthesis in proliferating cells. Adenine molecule itself acts biological modulator in inflammation and cell death. In the previous report, we showed that adenine induces apoptotic cell death of B16-F10 mouse melanoma cells by eliciting of PARP and caspase 3 cleavages. In this study, we examined the adenine effect on other apoptotic molecules affecting caspase activation in B16-F10 melanoma cells. Adenine treatment make pro-apoptotic molecules active states. Bax/Bcl-2 ratio was increased and phosphorylation of mTOR and Akt was decreased in a dose dependent manner. These results showed the possibility that Bax/Bcl-2, Akt and mTOR are engaged in adenine induced apoptosis of melanoma cells.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.41-55
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• 2004

Objective : To investigate the possible molecular mechanism (s) of melittin as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Methods : Growth inhibitory study, flow cytometry analysis, SDS-polyacrylamide gel electrophoresis and Western blot analysis, RT-PCR and in vitro caspases activity assay were performed. Results : Melittin treatment declined the cell viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Melittin treatment down-regulated the levels of Bcl-XS/L mRNA and protein expression of A549 cells, an anti-apoptotic gene, however, the those of Bax, a pro-apoptotic gene, were up-regulated. Melittin induced the proteolytic cleavage and activation of caspase-3 and caspase-9 protease in a dose-dependent manner without alteration of inhibitor of apoptosis proteins family and Akt expression. Western blot analysis and RT-PCR data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were also remained unchanged. Conclusions : Taken together, these findings suggest that melittin-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and melittin may have therapeutic potential in human lung cancer.