• Molecules and Cells
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• v.39 no.10
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• pp.742-749
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• 2016

The cancer chemo-preventive effects of equol have been demonstrated for a wide variety of experimental tumours. In a previous study, we found that equol inhibited proliferation and induced apoptotic death of human gastric cancer MGC-803 cells. However, the mechanisms underlying equol-mediated apoptosis have not been well understood. In the present study, the dual AO (acridine orange)/EB (ethidium bromide) fluorescent assay, the comet assay, MTS, western blotting and flow cytometric assays were performed to further investigate the pro-apoptotic effect of equol and its associated mechanisms in MGC-803 cells. The results demonstrated that equol induced an apoptotic nuclear morphology revealed by AO/EB staining, the presence of a comet tail, the cleavage of caspase-3 and PARP and the depletion of cIAP1, indicating its pro-apoptotic effect. In addition, equol-induced apoptosis involves the mitochondria-dependent cell-death pathway, evidenced by the depolarization of the mitochondrial membrane potential, the cleavage of caspase-9 and the depletion of Bcl-xL and full-length Bid. Moreover, treating MGC-803 cells with equol induced the sustained activation of extracellular signal-regulated kinase (ERK), and inhibiting ERK by U0126, a MEK/ERK pathway inhibitor, significantly attenuated the equol-induced cell apoptosis. These results suggest that equol induces mitochondria-dependent apoptosis in human gastric cancer MGC-803 cells via the sustained activation of the ERK1/2 pathway. Therefore, equol may be a novel candidate for the chemoprevention and therapy of gastric cancer.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.65-72
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• 2007

Objectives : In this study, we investigate that Euphorbiae lathyridis Semen extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Euphorbiae lathyridis Semen was extracted from the Semen of the plant using 80% Methanol. The Euphorbiae lathyridis Semen extract was treated to different concentrations for 24 hr, 4Shr or 72hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Westem blot. Results : Exposure to Euphorbiae lathyridis Semen extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Euphorbiae lathyridis Semen extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Euphorbiae lathyridis Semen extract induces DNA fragmentation in HT-29 cells. Furthermore, Euphorbiae lathyridis Semen extract induces cell apoptosis through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion : Euphorbiae lathyridis Semen extract induces apoptosis in human colon cancer cells, therefore, we suggest that Euphorbiae lathyridis Semen extract can be used as a novel class of anti-cancer drugs.

• The Journal of Dong Guk Oriental Medicine
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• v.11
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• pp.52-57
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• 2008

Objectives. In this study, we investigate that methanol extract of Euphorbiae lathyridis Semen contributes to growth inhibitory effect on the HT-29 human colon cancer cells. Methods. Euphorbiae lathyridis Semen (ELS) was extracted with 80% methanol. HT-29 cells were treated with different concentrations of ELS extract for 24-72 hrs. Growth inhibitory effect was determined by MTT assay. Cell apoptosis was determined by surveying caspases cascades activation using Western blot. Cell cycle arrest was analyzed by flow cytometry with PI staining. Results. Exposure to ELS extract showed in inhibitory effects on HT-29 cell growth as a dose-dependent manner. Cell growth inhibition by ELS extract was related with induction of cell apoptosis with DNA fragmentation through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion. ELS extract significantly inhibited cell growth and induced cell apoptosis in HT-29 human colon cancer cells, therefore, These results suggest that ELS extract can be used as chemoprevention agent of colon cancers.

• BMB Reports
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• v.45 no.9
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• pp.526-531
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• 2012

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-${\alpha}$)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. TNF-${\alpha}$-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-${\alpha}$-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-${\alpha}$-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.

• Herbal Formula Science
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• v.25 no.3
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• pp.349-362
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• 2017

Objectives : We investigated whether the components of Ailanthus altissima induced apoptotic cell death in Jurkat acute lymphoblastic leukemia (ALL) cells. Methods : Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. Results : Upon treatments with Ailanthus altissima, the concentration-dependent inhibitions of cell viability were observed as compared to untreated control group. The capability of Ailanthus altissima to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly(ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Ailanthus altissima also caused apoptosis as measured by cell morphology and DNA fragmentation. Conclusions : These results indicate that the increase of apoptotic cell death by Ailanthus altissima may be due to the inhibition of cell cycle in human Jurkat lymphocytes. Conclusively, these current and further findings will provide novel approaches to understanding and treating major diseases.

• Biomedical Science Letters
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• v.17 no.3
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• pp.177-184
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• 2011

Potassium cyanate (KOCN) is an inorganic compound and induces the carbamylation of proteins with cytotoxic effects on human cells. Although there is a potential cytotoxic molecule, the role of KOCN on the apoptosis of cancer cell is not well understood. The present study investigated the effects of KOCN on the human colorectal cancer cell line, HCT 116 cells. To understand the anti-cancer effect of KOCN on HCT 116 cells, we examined alteration of apoptosis, the intracellular $Ca^{2+}$ concentration, the intracellular signaling pathway and generation of reactive oxygen species (ROS) in these cells treated with KOCN. The apoptosis of HCT 116 cells was induced by KOCN in a dose-dependent manner at 24 hours and 48 hours, respectively. The apoptosis was processed via the cleavage of poly ADP-ribose polymerase (PARP) and activation of caspase 3 in HCT 116 cells. KOCN induced the elevation of intracellular $Ca^{2+}$ concentration and changed the expressions of Bcl-2 family proteins. The pro-apoptotic Bax was continuously up-regulated, and the anti-apoptotic Bcl-2 was down-regulated by KOCN. KOCN also induced the hyperpolarization of mitochondria and the generation of ROS in HCT 116 cells. Taken together, these results indicate that KOCN induces the apoptosis of HCT 116 cells by disruption of $Ca^{2+}$ homeostasis and via mitochondrial pathway. This study provides the compound that may be used as a potent agent for the treatment of colorectal cancer.

• BMB Reports
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• v.48 no.2
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.71-80
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• 2012

Objective : The aim of this study is to evaluate anti-cancer effects of $Ampelopsisradix$ Extract (AE) on human lung cancer A549 cells. Method : The apoptotic activities and cell growth arrest activities of AE were measured using 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The molecules involved in apoptotic process were assessed by western blotting. Result : Treatment of AE potently reduced cell viability in a dose-dependent manner in A549 cells. AE (100-500 ${\mu}g/m{\ell}$) resulted in apoptosis via activation of caspase 9 following PARP cleavage in a time-and dose-dependent manner. The levels of Bax and Bad levels were increased by AE with a concomitant decrease of Bcl-xL. In addition, AE at the low dose (30 ${\mu}g/m{\ell}$) significantly inhibited cell growth in the presence of serum. Conclusion : AE has the potential as a therapeutic agent against lung cancer.

• Journal of Microbiology and Biotechnology
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• v.13 no.3
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• pp.394-399
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• 2003

The in vitro cytotoxic effects of newly synthesized copper (II) glycinate complex were investigated in two gastric cancer cell lines of SNU484 and SNU638 cells. The complex inhibited the growth and decreased the viability of both gastric cancer cells in a dose-dependent manner. Gastric cancer tells treated with the complex exhibited the features of apoptosis, as demonstrated by fragmentation of chromosomal DNA, activation of caspase-3-like enzyme, and cleavage of poly［ADP-ribose］ polymerase (PARP). With the treatment of copper (II) glycinate complex, the active form of caspase-3 was observed in SNU484 cells, but not in SNU638 cells, indicating that an alternative pathway of apoptosis might have been triggered in SNU638 cells. In conclusion, copper (II) glycinate complex induces apoptosis of SNU484 and SNU638 gastric cancer cells, and it is suggested that novel copper (II) glycinate complex is highly active against human gastric cancer cells.