• Natural Product Sciences
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• 제18권1호
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• pp.16-21
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• 2012

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has been shown to have the anti-angiogenic, anti-invasive and cancer chemopreventive activities, but the molecular mechanism of actions has not been fully elucidated yet. In the present study, we investigated the effect of honokiol on the growth inhibitory activity in cultured SNU-638 human gastric cancer cells. We found that honokiol exerted potent antiproliferative activity against SNU-638 cells. Honokiol also arrested the cell cycle progression at the G0/G1 phase and induced the apoptotic cell death in a concentration-dependent manner. The cell cycle arrest was well correlated with the downregulation of Rb, cyclin D1, cyclin A, cyclin E, and CDK4 expression, and the induction of cyclin-dependent kinase inhibitor p27. The increase of sub-G1 peak by honokiol was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, the cleavage of poly(ADPribose) polymerase, and the sequential activation of caspase cascade. These findings suggest the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of honokiol in human gastric cancer cell.

• Molecules and Cells
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• 제28권6호
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• pp.521-527
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• 2009

Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.

• Preventive Nutrition and Food Science
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• 제21권1호
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• pp.31-37
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• 2016

Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF ($100{\mu}g/mL$) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF ($200{\mu}g/mL$) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

• 한국식품영양과학회지
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• 제21권2호
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• pp.149-153
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• 1992

N-methyl-N'-nitro-N-nitrosoguanid me (MNNG)와 N-nitrosodimethylamine (NDMA)의 돌연변이 유발성 및 AZ-52l 사람의 위암세포의 성장에 미치는 녹황색 채소류의 저해 효과를 검토하였다. 26종의 시험 채소중 24종(92%)이 MNNG에 대한 항돌연변이성이 있었으며 (p<0.01, 0.05) 80%이상 저해 효과를 보인 시료는 들깻잎, 배추, 꽃양배추, 상치, 갓, 미나리, 들미나리, 당근, 우엉이었다. 한편 NDMA에 대해서도 실험채소중 85%가 항돌연변이성을 나타내었는데 (p<0.01, 0.05) 들깻잎, 배추, 케일, 콩나물, 양파는 80%이상의 저해 효과를 나타내었다. 위암세포의 성장 저해 효과에서는 들미나리와 들깻잎이 가장 저해 효과가 컸으며(97~100%) 콩나물과 미나리가 다음으로 효과가 컸었다(p< 0.001). 또한 브로콜리, 쑥갓, 풋고추, 고추잎, 시금치, 양배추, 고구마도 통계적인 유의성을 나타내며 암세포 성장을 억제하는 효과가 있었다(p< 0.01, 0.05).

• Journal of Gastric Cancer
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• 제3권2호
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• pp.88-92
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• 2003

Purpose: Mounting evidence suggests that alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell-cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human gastric cancer. The purpose of this study was to explore the expression status of phosphorylated Akt protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of phosphorylated Akt protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the phosphorylated Akt in 42 ($70\%$) of the 60 cancers. Normal gastric mucosal cells showed no or weak expression of phosphorylated Akt protein. Conclusion: Taken together, these results indicate that Akt is frequently activated in gastric adenocarcinoma cells and suggest that phosphorylayed Akt may play a role in the development of human gastric adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1817-1821
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• 2016

Objectives: To observed the effects of ginsenoside -Rh2 (GS-Rh2) on proliferation and apoptosis of side population (SP) human gastric cancer SGC-7901 cells. Materials and Methods: SGC-7901 SP and Non-SP cells were sorted by flow cytometry and assessed using the cck-8 method. Expression of apoptosis-related proteins Bax and Bcl-2 of SP before and after the intervention was determined by Western-blotting. Results: It was found that the proliferation of SP was significantly faster than that of NSP (P<0.05). In addition, GS-Rh2 inhibited proliferation of gastric cancer SP cells, induced cell cycle arrest and cell apoptosis, and changed the expression of BAX/Bcl-2 proteins in a time-dependent and concentration-dependent manner (P<0.05). Conclusions: With increase of GS-Rh2 dose, GS-Rh2 gradually inhibit the proliferation of SGC-7901 SP cells, which have high proliferation rate, through G1/G0 phase arrest, followed by apoptosis which involves the up-regulation of Bax and the down-regulation of Bcl-2.

• 약학회지
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• 제38권3호
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• pp.311-321
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• 1994

Anticancer effects of Aloe on sarcoma 180 in ICR mouse or human cancer cells were determined. Sarcoma 180 cells were inoculated subcutaneously into male ICR mouse to determine effect of Aloe on tumor gowth, or inoculated intraperitoneally into male ICR mouse to determine effect of Aloe on life span prolongation, followed by oral administration of Aloe vera(10 mg/kg/day, 50 mg/kg/day) or Aloe arborescens(10 mg/kg/day, 100 mg/kg/day) once a day for 14 days. The administration of Aloe vera or Aloe arborescens did not suppress tumor growh. However the life span of ICR mouse was prolonged to 19%(p<0.05), 22%(p<0.05) and 32%(p<0.05) by administration of Aloe vera 10 mg/kg/day, Aloe vera 50 mg/kg/day, and Aloe arborescens 100 mg/kg/day, respectively. To determine anticancer effect of Aloe in vitro, Aloe extract was added to the culture of human gastric cancer cells(SNU-1) and colorectal cancer cells(SNU-C2A), and concentration of Aloe to inhibit cancer cell growth was determined using MTT(3-[ 4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cytotoxicity assay. High $ID_{50}$ values of Aloe vera and Aloe arborescens against gastric cancer cell line(SNU-1) and colorectal cancer cell line(SNU-C2A) suggest that Aloe gel does not have anticancer effect on these specific human cancer cells although high concentration of Aloe inhibited growth of human cancer cells significantly.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.397-405
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• 2017

MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (${\sim}20{\mu}M$), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than $20{\mu}M$, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.

• 동의생리병리학회지
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• 제27권1호
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• pp.92-98
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• 2013

Bee Venom(below BV) has been used in alternative medicine to treat the diseases, such as pain diseases. BV contains a variety of peptides, including melittin, apamin, adolapin, MCD peptide, enzymes(i.e. PLA2), amines(i.e. histamine and epinephrine), and nonpeptide components. The two main components of BV are melittin and PLA2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the depress of cancer cell. Melittin and PLA2 have been reported to induce apoptosis and to possess anti-cancer effects and neurite outgrowth in PC12 cells. Analysis of proliferation was confirmed by MTT assay. BV decreased cell number through dose- and duration-dependent manner and these effects are apparent at a concentration of 3 ${\mu}g/ml$. To observe which signaling molecules will be activated by BV, phosphorylation of ERK, p38 MAPK, JNK and ERM were examined by Western blot analysis. To study the long term effect of BV in human gastric adenocarcinoma cell lines, the image of cells treated with BV for 4 days were obtained. BV was shown to exhibit anti-cancer activity in human gastric adenocarcinoma cell lines at a broad range of concentrations of 3 ${\mu}g/ml$. ERK, p38 MAPK and JNK were found to increase in BV treated cells. However, ERM which known to be involved in the cell death, was gradually decreased to 30minutes after addition 3 ${\mu}g/ml$ of BV. These results provide a possible BV-induced inhibitory signal for cancer proliferation that is initiated by the decrease in ERM activity. Moreover, it is likely that the activation of ERK, p38 MAPK and JNK are required for the BV-induced inhibition of cancer proliferation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6753-6759
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• 2015

Background: Loss of function of the p53 gene is implicated in defective apoptotic responses of tumors to chemotherapy. Although the pro-apoptotic roles of eugenol and capsaicin have been amply reported, their dependence on p53 for apoptosis induction in gastric cancer cells is not well elucidated. The aim of the study was to elucidate the role of p53 in the induction of apoptosis by eugenol and capsaicin in a human gastric cancer cell line, AGS. Materials and Methods: AGS cells were incubated with or without various concentrations of capsaicin and eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling, annexin V and expression of apoptosis related proteins Bax, Bcl-2 ratio, p21, cyt c-caspase-9 association, caspase-3 and caspase-8 were studied. Results: In the presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol. However, silencing of p53 significantly abrogated apoptosis induced by capsaicin but not that by eugenol. Western blot analysis of pro-apoptotic markers revealed that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3 even in the absence of p53. Conclusions: Unlike capsaicin, eugenol could induce apoptosis both in presence and absence of functional p53. Agents which can induce apoptosis irrespective of the cellular p53 status have immense scope for development as potential anticancer agents.