• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.88.2-88.2
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• 2008

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.42.2-42.2
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• 2007

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• The Korea Journal of Herbology
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• v.21 no.1
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• pp.33-42
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• 2006

Objectives : The purpose of this study was to investigate the anticancer effects of Bodusan (BDS) on SNU-1 cells, a human gastric cancer cell line. Methods : To study the cytotoxic effect of BDS on SNU-1 cells, the cells were treated with various concentrations of BDS and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. The typical signs of apoptosis, was examined by western blot analysis. BDS-induced MAPK activation was also examined by Western blot for phosphorylated ERK and p38. Results : BDS reduced proliferation of SNU-1 cells in a dose-dependent manner and decreased procaspase 3 level in a dose-dependent manner and induced the clevage of PARP at concentration > 500 ${\mu}g/ml$. BDS also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol and reducing the level of anti-apoptotic Bcl-2. BDS significantly decreased ERK phosphorylation and increased p38 phosphorylation in a dose-dependent manner. Futhermore, BDS treatment up-regulated p53 and p21waf expression in a dose-dependent manner. Conclusion : BDS-induced apoptosis is MAP kinase-dependent apoptoric pathway and arrested SNU-1 cells at the G0/G1 of cell cycle. These results suggest that BDS is potentially useful as a chemotherapeutic agent in human gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5895-5900
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• 2013

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.1
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• pp.20-27
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• 2014

Our study is investigated the effects of Nelumbo nucifera root extract on HT-29 colon cancer cells. The anti-proliferative effect of 70% ethanol extract from Nelumbo nucifera root on HT-29 colon cancer cells was identified based on cell viability, Hoechst 33342 nuclear staining, apoptosis analysis, Western blotting and RT-PCR analyses. In our study, Nelumbo nucifera root extract inhibited the growth of HT-29 colon cancer cells in a dose-dependent manner. Concomitant activation of the mitochondria-dependent apoptotic pathway of HT-29 colon cancer cells by Nelumbo nucifera root extract occurred via modulation of Bax and Bcl-2 expressions, which activated cleavage of caspases-3 and -9. The findings of this study indicate that Nelumbo nucifera root extract induces apoptosis in HT-29 colon cancer cells, and this phenomenon is occurs via the death receptor-mediated and mitochondria-mediated apoptotic pathways.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.41-47
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• 2019

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

• Toxicological Research
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• v.17 no.3
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• pp.215-223
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• 2001

Cadmium is an ubiquitous toxic metal and chronic exposure to cadmium results in the accumulation of cadmium in the liver and kidneys. In contrast, acute exposure leads to damage mainly in the liver. Apoptosis induced by cadmium has been shown in many tissues in vivo and in cultured cells in vitro. However, the molecular mechanism of cadmium-induced apoptosis is not clear in hepatocyte. To investigate the induction of apoptosis in the hepatocyte, we used mouse hepatoma cell line, Hepalclc7 cells, and analysed the molecules that involved in cadmium-induced apoptosis. Cadmium induced the genomic DNA fragmentation, PARP cleavage, and activation of caspase-3 like protease. Caspase-9 cysteine protease was activated in a time-dependent manner but caspase-8 cysteine protease was not significantly activated in cadmium-treated Hepalclc7 cells. Cadmium also induced mitochondrial dysfunction including cytochrome c release from mitochondria, change oj mitochondrial membrane potential tranition, and tranlocation of Bax Protein into mitochondria. These results strong1y indicated that the signal Pathway of apoptotic death in cadmium-treated Hepalclc7 cells is modulated by caspase cascade via mitochondria.

• 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.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.62-67
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• 2012

TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.266-274
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• 2022

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.