• 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.

• Preventive Nutrition and Food Science
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• 제10권2호
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• pp.167-171
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• 2005

The anticancer and apoptotic effect of chloroform extract from 24 month-fermented doenjang were investigated in AGS human gastric adenocarcinoma cells. The chloroform extract of 24 month-fermented doenjang inhibited the AGS gastric cancer cell growth in a dose-dependent manner. It has been confirmed by observing the cell distribution under inverted microscope. Approximately, 48 hour treatment of $100\;{\mu}g/mL$ doenjang extract inhibited AGS cancer cell growth by $76.7\%$, respectively. The growth inhibition may be caused by apoptosis of AGS cancer cells after 48 hour treatment of 24 month-fermented doenjang extract. It has been demonstrated by cell cycle arrest that revealed the shift from $G_2+M\;to\;G_0+G_1$ phase and the formation of apoptotic bodies. The fermentation period playa critical role in cell cycle arrest, in which 24 month-fermented doenjang extract was more effective than 12 month-fermented doenjang extract. The treatment of 24 month-fermented doenjang extract for 48 hours has induced intercellular Bax and decreased Bcl-2 level, indicating that it may regulate the expression level of Bax/Bcl-2 proteins. Thus, 24 month-fermented doenjang extract seems to have anticancer effect via cancer cell growth inhibition induced by apoptosis process.

• 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.

• 대한약침학회지
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• 제15권3호
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• pp.31-38
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• 2012

Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic functions in many organs. Objective: The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Methods: The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose) polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers ($Gd^{3+}$ or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Results: The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by $Gd^{3+}$ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. Conclusions: These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.

• 대한한의학방제학회지
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• 제30권2호
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• pp.59-66
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• 2022

Objectives : This study is to investigate whether Carthami flos exhibits a synergistic effect on the apoptotic effect of doxorubicin on human gastric cancer cells. Methods : We used AGS, a human gastric cancer cell line. To investigate the apoptotic efficacy of doxorubicin and Carthami flos, MTT and CCK-8 methods were used. To confirm apoptosis, cell cycle and mitochondrial membrane potential changes were confirmed. To investigate the mechanism of apoptosis, the reactive oxygen species (ROS) experiment was performed. Results : 1. Doxorubicin or Carthami flos induced cell death in the human gastric cancer cell line AGS. 2. Carthami flos showed a synergistic effect of cell death by doxorubicin. 3. The cell cycle and mitochondrial membrane potential changes revealed that cell death was apoptosis. 4. Apoptosis was related to reactive oxygen species (ROS) generation. Conclusions : This result shows the anticancer synergistic effect of Carthami flos in gastric cancer cells, and is considered to be an important basis for the development of anticancer drugs for Carthami flos.

• 대한의생명과학회지
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• 제28권2호
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• KSBB Journal
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• 제32권2호
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• pp.83-89
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• 2017

Gamma (${\gamma}$)-oryzanol is a substance abundant in rice, which is widely cultivated in Asian countries. In this study, we evaluated the effect of ${\gamma}$-oryzanol treatment on proliferation and apoptosis of AGS human gastric carcinoma cells. AGS cells were treated with ${\gamma}$-oryzanol for 72 h in a dose dependent manner. Treatment of ${\gamma}$-oryzanol (50, 100, and $200{\mu}g/mL$) resulted in decreased AGS cell proliferation and increased number of cells in the sub-G1 population. Additionally, apoptotic cells were investigated by annexin V staining and mitochondrial membrane potential assays. Our results indicated that ${\gamma}$-oryzanol treatment increased the number of annexin V-positive cells and depolarized cells. This demonstrated that ${\gamma}$-oryzanol is effective for the induction of apoptosis in AGS cells. We next examined the expression of promising anticancer drug target molecules, including PTEN and HSP90. We found that treatment of ${\gamma}$-oryzanol induced the expression of PTEN in AGS cells. Under the same treatment conditions, ${\gamma}$-oryzanol reduced the expression of HSP90 in AGS cells. These results suggest that ${\gamma}$-oryzanol-induced apoptosis was accompanied by changes in regulation of PTEN and HSP90 in AGS cells. Taken together, ${\gamma}$-oryzanol could be used as a functional substance for the prevention of gastric cancer.

• Korean Journal of Acupuncture
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• 제29권2호
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• pp.271-289
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• 2012

Objectives : Ganoderma lucidum(Ganoderma or lingzhi, 靈芝) is a well-known oriental medical mushroom containing many bioactive compounds. The possible mechanisms involved in its effects on cancer cells remain to be elucidated. In the present study, the anti-proliferative and apoptotic activities of the G. lucidum ethanol extract(GEE), in AGS human gastric cancer cells were investigated. Methods : It was found that exposure of AGS cells to GEE resulted in the growth inhibition in a dose and time dependent manner as measured by trypan blue count and MTT assay. The anti-proliferative effect of GEE treatment in AGS cells was associated with morphological changes and formation of apoptotic bodies, and the flow cytometry analysis confirmed that GEE treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptosis of AGS cells by GEE were connected with a concentration and time-dependent up-regulation of tumour necrosis factor-related apoptosis-inducing ligand(TRAIL) expression. Results : The levels of XIAP and survivin expression, members of IAP family proteins, were gradually down-regulated by GEE treatment. However other members of IAP family proteins such as cIAP-1 and cIAP-2 remained unchanged in GEE-treated AGS cells. GEE treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9 and a concomitant degradation of poly(ADP-ribose) polymerase(PARP) protein, a caspase-3 substrate protein. Additionally, GEE-induced apoptosis was associated with the inhibition of Akt activation in a concentration and time-dependent manner, and pre-treatment with LY294002, a phosphoinositide 3-kinase(PI3K)/Akt inhibitor, significantly increased GEE-induced growth inhibition and apoptosis. Conclusions : Therefore, G. lucidum has a strong potential as a therapeutic agent for preventing cancers such as gastric cancer cells.

• 생명과학회지
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• 제25권8호
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• pp.849-860
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• 2015

본 연구에서는 한약재로 널리 사용되는 건칠, 유근피 및 신석 추출물의 항암 활성을 조사하였다. 생쥐 유래 정상세포(RAW 264.7 대식세포 및 C2C12 근아세포)에서는 건칠, 유근피 및 신석 단독 및 복합 처리에 의하여 유의적인 세포생존율의 억제 현상은 관찰 할 수 없었다. 그리고 건칠, 유근피 및 신석의 복합 처리는 단독 처리군에 비하여 AGS 위암세포의 생존력을 유의적으로 억제하였으나, 폐암(A549), 대장암(HCT116), 간암(Hep3B) 및 방광암(T24) 세포에서는 그 효과가 미비하였다. 아울러 이러한 AGS 위암세포 선택적 생존 억제력은 apoptosis 유도와 밀접한 연관성이 있음을 염색질의 응축 현상, DNA 단편화 및 annexin-V 염색에 의한 flow cytometry 분석을 통하여 확인하였다. 건칠, 유근피 및 신석의 복합 처리는 Fas 및 Fas legand의 발현을 증가시켰으며, XIAP, cIAP-1 및 survivin과 같은 IAP family 단백질과 anti-apoptotic Bcl-xL의 발현은 저하시켰다. 복합 처리는 또한 mitochondrial membrane potential의 손실과 caspases (-3, -8 및 -9)의 활성에 PARP 단백질의 분절화를 유도하였다. 그러나 이러한 복합 처리에 의한 AGS 세포에서 관찰된 세포독성 및 apoptosis 유도 효과는 pan-caspases inhibitor인 z-VAD-fmk의 선처리에 의하여 차단되었다. 이상의 결과는 건칠, 유근피 및 신석의 복합 처리에 의한 AGS 위암세포 선택적 apoptosis 유도가 caspase 의존적으로 일어나고 있음을 보여주는 결과이며, in vivo 모델을 이용한 후속 연구가 진행되어야 할 것이다.

• Preventive Nutrition and Food Science
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• 제4권2호
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• pp.107-112
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• 1999

Effect of solvent extracts and juice supernatants from kimchis on the growth of various human cancer cells was studied, comparing with the actions on the normal cells. Inhibitory effect of kimchi extracts on[3H] thymidine incorporation n cancer cells was also investigated. The methanol extract, hexane extract and methanol soluble fraction (MSF) of 3-week fermented kimchi did not have growth inhibitory effect on Ac2F rat normal liver cells at the concentrations of 0.5~2%. However, marked decrease in the growth of AGS human gastric cancer cells was shown by the treatment of those extacts. The juice from the kimchi samples also suppressed the growth of K-562 human leukemia cells and MG-63 human osteosarcoma cells. Especially, the juice of 3-week fermented kimchi exhibited the strong growth inhibitory effect in MG-63 human osteosarcoma cells. At the photomicrographs, growth inhibition and morphological change of the cells treated with kimchi juice were observed. And the solvent extracts of 3-week fermented kimchi suppressed the growth of cancer morethan the extracts or juices from fresh and 6-week fermented kimchi. When AGS human gastric cancer cels were treated with the extracts of 3-week fermented kimchi, [3H] thymidine incorporation in the cells also decreased. These results showed that kimchi extracts and juices had growth inhibitory effects on human osteosarcoma, leukemia and gastric cancer cells, but had no toxicity to the normal cells. We suggest that kimchi might have anticancer effect in part due to inhibition of the growth and DNA synthesis of cancer cells.