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

• Biomolecules & Therapeutics
• /
• v.31 no.2
• /
• pp.219-226
• /
• 2023

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.5
• /
• pp.2121-2127
• /
• 2012

Objective: Deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) mutants have been reported to exert suicide gene effects in combined gene/chemotherapy of cancer. Here, we aimed to further evaluate the capacity of the mutanted enzyme and its potential for inhibiting cancer cell growth. Methods: We altered the sequence of the last 10 amino acids of Dm-dNK to perform site-directed mutagenesis and constructed active site mutanted Dm-dNK (Dm-dNKmut), RT-PCR and western bloting studies were used to reveal the expression of lentivirus mediated Dm-dNKmut in a breast cancer cell line (Bcap37), a gastric cancer cell line (SGC7901) and a colorectal cancer cell line (CCL187). [3H]-labeled substrates were used for enzyme activity assays, cell cytotoxicity was assessed by MTT assays, cell proliferation using a hemocytometer and apoptosis induction by thenannexin-V-FITC labeled FACS method. In vivo, an animal study was set out in which BALB/C nude mice bearing tumors were treated with lentivirus mediated expression of Dm-dNKmut with the pyrimidine nucleoside analog brivudine (BVDU, (E)-5-(2-bromovinyl)-(2-deoxyuridine). Results: The Dm-dNKmut could be stably expressed in the cancer cell lines and retained its enzymatic activity. Moreover, the cells expressing Dm-dNKmut exhibited increased sensitivity in combination with BVDU, with induction of apoptosis in vitro and in vivo. Conclusion: These findings underlined the importance of BVDU phosphorylated by Dm-dNKmut in transduced cancer cells and the potential role of Dm-dNKmut as a suicide gene, thus providing the basis for future intensive research for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1511-1514
• /
• 2012

Objective: The present study aimed to investigate the influence of siRNA interference with a proliferation-inducing ligand (APRIL) gene on gastric carcinoma sgr-7901 cell apoptosis. Correlations between APRIL silencing and tyrosine kinase (trka) expression were also explored. Methods: Two APRIL-silencing siRNA vectors were constructed, and transfected into human gastric carcinoma sgr-7901 cells, expression before and after transfection being detected using RT-PCR and western blot analyses. The expression of 15 trka genes was detected using RT-PCR and apoptotic rates of sgr-7901 were assessed by flow cytometry. Results: The expression levels of receptor trka genes were significantly decreased, and the apoptotic rate of sgr-7901 was significantly increased after transfection (P < 0.05). Conclusion: APRIL gene silencing can increase the apoptotic rate of gastric carcinoma cells, and inhibit the expression of receptor trka genes. There is a correlation between the signaling pathways of APRIL and trka.

• The Journal of Internal Korean Medicine
• /
• v.28 no.2
• /
• pp.321-332
• /
• 2007

Objectives : Anticancer and immune-modulating effects of several Korean medical prescriptions including Yukgunja-tang, Bohwa-tang, Sogam-Won, and Kamiboa-tang were investigated. Methods : In vitro anti-cancer effects were measured by cytotoxicity MTT assay using SNU-1 gastric cancer cell lines, In vivo anti-cancer effects were measured by increased life span of S-180 sarcoma-injected ICR mouse. Immune-modulating effects were analyzed by measuring hemagglutinin titer, appearance of rosette forming cells, lymphocyte proliferation, and phagocytic index in methotrexate-pretreated mice. Results : In vitro assay showed that only Sogam-won showed cytotoxic effect with $IC_{50}$ of 87.9 ${\mu}g/ml$. All other prescriptions showed no cytotoxic effects against SNU-1 gastric cancer cell line. However, in vivo assay showed that Sogam-won showed lowest anti-cancer effects in contrast to its highest cytotoxic effects, Kamiboa-tang, which showed no cytotoxic effect, showed the highest in vivo anticancer effects, with increased life span of 140%. Kamiboa-tang showed significant immune-enhancing activities by significantly increasing rosette forming cells, lymphocyte proliferation, and phagocytic index in methotrexate-pretreated mice (P<0.05). Conclusion : The anticancer effect of Kamiboa-tang is not mediated by direct inhibition of cancer cells but is mediated by improving immune reactions against cancer cells.

• Herbal Formula Science
• /
• v.27 no.1
• /
• pp.53-63
• /
• 2019

Objectives : In this study, we investigated the combination effects of Cinnamomi cortex Ethanol Extract (CcEE) and hyperthermia in the human AGS gastric cancer cell line. Methods : AGS cells were treated with the indicated concentrations of CcEE (0, 50 or $60{\mu}g/mL$) for 1h prior to hyperthermia. And then incubated for a further 30 min at the indicated temperatures (37, 42 or $43^{\circ}C$) in a humidified incubator containing 5% $CO_2$ or a thermostatically controlled water bath for hyperthermia. The cell viability was measured by MTT assay, Morphology assay and Trypan blue assay. To investigate the possible molecular signaling pathways, the activation of mitogen-activated protein kinase (MAPK) proteins (ERK, p38 and JNK) and expression of various anti-apoptotic proteins such as Caspase-3, Caspase-9, p53, Cyclin D1 and MMP-2 were assessed by Western blot analysis. In addition, Annexin V and 7-amino-actinomycin D (7-AAD) staining was performed to examine the apoptotic mechanism. Results : Combination of CcEE with hyperthermia effectively suppressed the cell viability and changed cellmorphology compared with CcEE or hyperthermia treatment alone. Combined treatment also abated the expression of Caspase-3, Caspase-9, Cyclin D1 and MMP-2. Whereas, the expression level of p53 was up-regulated by co-treatment. Moreover, combination treatment enhanced phosphorylation of ERK, p38 and JNK. In addition, this combination increased anti-cancer effect by inducing cell death through the apoptosis. Conclusions : Taken together, all these findings suggest that the combination treatment with CcEE and hyperthermia may have therapeutic potential as a promising approach to patients with stomach cancer.

• Journal of Pharmaceutical Investigation
• /
• v.37 no.5
• /
• pp.305-309
• /
• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

• Journal of Gastric Cancer
• /
• v.20 no.4
• /
• pp.408-420
• /
• 2020

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions: CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

• Korean Journal of Oriental Medicine
• /
• v.18 no.1
• /
• pp.85-92
• /
• 2012

Objective : The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of 5-Fluorouracil (5-FU) in human gastric adenocarcinoma cells (AGS). Method : We used human gastric adenocarcinoma cell line, AGS cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle (sub G1) analysis was done the AGS cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with 100 ${\mu}g/ml$ Sophorae Radix. Result : Sophorae Radix inhibited the growth of AGS cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in AGS cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with 5-FU markedly inhibited the growth of AGS cells compared to Sophorae Radix or 5-FU alone. After 3 days treatment of AGS cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Conclusion : Our findings provide insight into unraveling the effects of Sophorae Radix in human gastric adenocarcinoma cells and developing therapeutic agents against gastric cancer.

• The Journal of Korean Medicine
• /
• v.25 no.4
• /
• pp.79-89
• /
• 2004

Saussurea lappa and Taraxacum mongolicum have been used for herbal medicinal treatments against cancers in East Asia. We performed this study to understand the molecular basis underlying the anti-tumor effects of two herbs and analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules by using an AGS gastric cancer cell line. The treatments of Saussurea lappa dramatically reduced cell viabilities in a dose and time-dependent manner, but Taraxacum mongolicum did not. FACS analysis and Annexin V staining assay also showed that Saussurea lappa induces apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Saussurea lappa increased expression of the p53 and its downstream effector p21/sup Waf1/, and that the both increased expression of apoptosis related Bax and cleavage of active caspase-3 protein. We also confirmed the translocation of Bax to mitochondria Collectively, our data demonstrate that Saussurea lappa induces growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.