We have reported the case of a patient diagnosed as having advanced gastric cancer at the age of 88 years old. An endoscopy revealed a type-2 gastric cancer of 25 x 30 mm in the lesser curvature of the middle stomach body and an IIa gastric cancer with T2 SS and cardiac accessory lesions. Both the type-2 and IIa lesions were defined as tub1 with surrounding atrophic gastritis and entero-epithelium metaplastic carcinoma. Considering the patient's age and her desire not to receive cancer treatment, we prescribed laughter therapy as recommended by the Society for Healing Environment. The program was implemented in a laughter-inducing environment and consisted of five stages: (1) Making the patient feel safe, (2) Relaxing the patient, (3) Increasing the effectiveness, (4) Improving her condition and (5) Increasing her joy of living. One year and seven months later, an endoscopy of the lesser curvature of the middle stomach body indicated that the lesions clearly improved with a morphological reduction into IIa + IIc masses. A tissue biopsy revealed that nucleus abnormality clearly improved from the initial diagnosis, with no irregularity in size. The suspected lesion was localized to a limited area near the stomach wall. Although partial gastric adenocarcinoma was suspected, the cancers turned into gastric adenoma, atrophic gastritis, and enteroepithelium metaplastic carcinoma. Now, five years after the initial diagnosis, she maintains a good condition. Laughter, one of our casual behaviors, has the effect of reducing the stress experienced by the human body. Laughter is expected to become alternative medicine in the future, and we hope to see more reports and evidence on soothing therapies using laughter.

FSK88, a forskolin derivative, was extracted and purified from cultured tropical plant roots, Coleus forskohlii. Our previous studies have demonstrated that FSK88 can inhibit HL-60 cell proliferation and induce the differentiation of HL-60 cells to monocyte macrophages. In this study, we showed that FSK88 can induce apoptotic death of human gastric cancer BGC823 cells in a dose- and time-dependent manner.Results showed that FSK88-induced apoptosis was accompanied by the mitochondrial release of cytochrome c and activation of caspase-3 in BGC823 cells. Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable of preventing the FSK88-induced caspase-3 activity and apoptosis. FSK88-induced apoptosis in human gastric cancer BGC823 cells was also accompanied by the up-regulation of Bax, Bad and down-regulation of Bcl-2. Theses results clearly demonstrated that the induction of apoptosis by FSK88 involved multiple cellular and molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family genes, mitochondrial membrane potential (Deltapsi(m)), cytochrome c, and caspase-3, participate in the FSK88-induced apoptotic process in human gastric cancer BGC823 cells.

Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.

The aim of this study is to evaluate the association between adherence to Mediterranean diet (MD) and gastric cancer (GC). A case-control study was carried out at the Fondazione Policlinico 'A. Gemelli' (Rome, Italy) from 2003 to 2015. A total of 223 incident cases and 223 controls were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on more than 25 food items. The association between adherence to MD and risk of GC was quantified by calculating Odds Ratios (OR) and 95% confidence intervals (CI). The analysis reports that a higher adherence to MD is associated with a reduced risk of GC (OR: 0.70; 95% CI: 0.61-0.81). A high consumption of vegetables (OR: 0.34; 95% CI: 0.14-0.85), legumes (OR: 0.13; 95% CI: 0.06-0.29), and fish (OR: 0.33; 95% CI: 0.15-0.68), as well as low consumption of meat (OR: 0.29; 95% CI: 0.10-0.85) and alcohol (OR: 0.46; 95% CI: 0.24-0.90) are consistently related to a lower risk of GC. Our study indicates a protective role of the MD eating pattern and MD individual components against GC. Our results showed a beneficial role of high vegetable, legume, and fish consumption, along with low intake of alcohol and meat in the development of GC.

We investigated the effects of a water-soluble extract of Maitake (Grifola frondosa), a Japanese edible mushroom, on the proliferation and cell death of four human gastric cancer cell lines (TMK-1, MKN28, MKN45 and MKN74). The Maitake extract (ME) inhibited the proliferation of all four cell lines in a time-dependent manner. The inhibition was most pronounced in TMK-1 cells, which exhibited up to 90% inhibition after treatment with 10% ME for 3 days. Staining of ME-treated TMK-1 cells with Hoechst 33258 revealed increased numbers of nuclear condensations and apoptotic bodies. Induction of apoptosis was confirmed by fluorescence-activated cell sorting analyses. Western blot analyses of TMK-1 cells after ME treatment revealed increases in intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose) polymerase, but no expression of p21 or Bax. The caspase-3 protease activities in lysates of TMK-1 cells treated with 1% or 10% ME were about three times higher than those in control cells. The proliferation of TMK-1 cells was hardly affected by the caspase-3 inhibitor z-DEVD-fmk. Taken together, these results suggest that ME induces apoptosis of TMK-1 cells by caspase-3-dependent and -independent pathways, resulting in potential antitumor effects on gastric cancer.

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0-G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0-G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

In this study, a high yield of crude polysaccharide (16.73± 0.756%) was extracted from the spent mushroom substrate of Lentinus edodes using a hot alkali extraction method. Two groups of polysaccharides (designated as LSMS-1 and LSMS-2) were obtained from the crude extract by size exclusion chromatography (SEC), and their molecular characteristics were examined by a multiangle laser-light scattering (MALLS) and refractive index detector system. The weight-average molar masses of LSMS-1 and LSMS-2 were determined to be 6.842 × 106 and 2.154 × 106 g/mol, respectively. The SEC/MALLS analysis revealed that the molecular shapes of LSMS-1 and LSMS-2 were sphere-like forms in aqueous solution. Carbohydrate composition analysis using chromatography--mass spectrometry revealed that they were both acid heteropolysaccharides. LSMS-1 comprised mainly glucose and galacturonic acid, whereas LSMS-2 mainly consisted of xylose and glucuronic acid. Fourier transform infrared spectral analysis of the purified fractions revealed typical characteristic polysaccharide groups. In addition, MTT assays with refined polysaccharide doses of 25, 50, 100, 200, and 400 µg/mL suggested that both of the polysaccharide fractions exhibited antiproliferative activity against 6 tested human tumor cell lines in a concentration-dependent manner, and LSMS-2 had better anticancer capacity in vitro than LSMS-1. The inhibition ratio of LSMS-2 against A549 human lung cancer cells, the SGC7901 gastric cancer cell line, MCF-7 breast cancer cells, the U937 histiocytic lymphoma cell line, and the MG-63 human osteosarcoma cell line reached 43.55%, 29.97%, 19.63%, 18.24%, and 17.93%, respectively, at a concentration of 400 µg/mL.

The effect of oral vitamin C supplementation on intragastric ascorbate levels and gastric mucosal DNA damage as measured by the 32P-postlabelling assay was assessed in 43 patients. In patients with normal gastric mucosa, treatment with vitamin C resulted in elevation of intragastric ascorbate levels in all cases. In the presence of chronic atrophic gastritis, however, the effect was variable. Gastric mucosal DNA damage was decreased in 28 of the 43 patients after vitamin C supplementation (P = 0.01; Wilcoxon sign rank test). This supports epidemiological evidence that suggests vitamin C may exert a protective effect against the development of gastric cancer.

BACKGROUND: Helicobacter pylori (HP) is a gramnegative bacterium and well recognized as being the primary etiological agent responsible for the development of gastritis, dyspepsia, peptic ulcer disease and gastric cancer. In developing countries, a high prevalence of HP infection is associated with an increased incidence of gastric cancer. Thailand, however, while having a high prevalence of HP infections, has a lower than expected gastric cancer rate than other developing countries. It has been suggested that the diet and life style in Thailand may explain this discrepancy. MATERIALS AND METHODS: The in vitro susceptibility of 18 strains of HP to 20 extracts of spice and food plants used in Thai traditional medicine for the treatment of GI disorders was assessed. RESULTS: Methanol extracts of Myristica fragrans (aril) inhibited the growth of all HP strains with minimum inhibitory concentration (MIC) of 12.5 micrograms/ml; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had an MIC of 25.0 micrograms/ml; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50.0 micrograms/ml. Extracts with an MIC of 100.0 micrograms/ml included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf). CONCLUSION: Plants used in Thai traditional medicine to treat gastrointestinal ailments inhibit the growth of HP. These data indicate that these plants may have chemopreventative activities and thus may partly explain the reduced incidence of gastric cancer in Thailand.

GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of Grifola frondosa with novel sugar compositions and protein sequencing. The present study aims to investigate its effects on the cell cycle, differential proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle at S phase. GFG-3a treatment resulted in the differential expression of 21 proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM, HSP90AB1, and GRP78 involved in apoptosis and stress response. qRT-PCR and Western blot analysis also suggested that GFG-3a could increase the expressions of Caspase-8/-3, p53, Bax, and Bad while decrease the expressions of Bcl2, Bcl-xl, PI3K, and Akt1. These results indicated that the stress response, p53-dependent mitochondrial-mediated, Caspase-8/-3-dependent, and PI3k/Akt pathways were involved in the GFG-3a-induced apoptosis process in SGC-7901 cells. These findings might provide a basis to prevent or treat human gastric cancer with GFG-3a and understand the tumor-inhibitory molecular mechanisms of mushroom glycoproteins.

This study was designed to investigate the proliferation inhibition and apoptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05). For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05). 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01). The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05), which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901.

Loss of parietal cells initiates the development of spasmolytic polypeptide-expressing metaplasia (SPEM), a precancerous lesion in stomach. CD44 variant (CD44v) which enhances the ability to defend against reactive oxygen species (ROS) in epithelial cells is expressed de novo in SPEM of K19-Wnt1/C2mE mice, a transgenic model of gastric tumorigenesis, and is required for the efficient development of SPEM and gastric tumor in these animals. The role of ROS and its downstream signaling in CD44-dependent gastric tumorigenesis has remained unknown, however. With the use of the K19-Wnt1/C2mE mouse we now show that parietal cells in the inflamed stomach are highly sensitive to oxidative stress and manifest activation of p38MAPK signaling by ROS. Oral treatment with the antioxidant ascorbic acid or genetic ablation of the Ink4a/Arf locus, a major downstream target of ROS-p38MAPK signaling, inhibited parietal cell loss and the subsequent gastric tumorigenesis. Our results indicate that signaling activated by oxidative stress in parietal cells plays a key role in CD44-dependent gastric tumorigenesis.

OBJECTIVE: To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. METHODS: Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H202 were evaluated by spectrophotography. RESULTS: Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 microm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 microm x s(-1) x V(-1) x cm(-1). The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H202) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H202 group. CONCLUSIONS: Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

PURPOSE:Natural product Poria cocos possesses antitumor effect. This study will explore the molecular mechanism of Poria cocos combined with chemotherapy in the inhibition of gastric cancer cell EMT process.

METHODS:The experiment was divided into blank control group, Poria cocos group, oxaliplatin group and Poria cocos combined with oxaliplatin group. Scratch and Transwell assay were used to detect cell migration and invasion respectively. RT-qPCR and Western Blot analyses were used to detect mRNA and protein expression of the epithelial-mesenchymal transition (EMT) related factors including Snail, Twist, Vimentin, E-cadherin and N-cadherin respectively. Morphologic assessment was performed with HPIAS-1000 automated image analysis system.

RESULTS:The migration and invasion abilities of gastric cancer cells in the Poria cocos combined with oxaliplatin group were significantly decreased (P < 0.01). The mRNA and protein expression of Snail, Twist, Vimentin and N-cadherin were significantly decreased while the mRNA and protein expression of E-cadherin were significantly increased (P < 0.01) compared with blank control group. Nude mice model of gastric cancer was successfully established. Poria cocos combined with oxaliplatin could significantly inhibit gastric tumor progression. The expression of EMT related factors were consistent with in vitro study. Morphologic assessment showed that the nucleus area, perimeter, mean diameter, volume, long diameter and shape factor in the Poria cocos combined with oxaliplatin group were significantly different compared with the blank control group (P < 0.01) but not significantly different compared with the normal control.

CONCLUSIONS:Poria cocos combined with oxaliplatin could significantly inhibit the migration and invasion of gastric cancer cells. Through both in vitro and in vivo studies, it is confirmed that Poria cocos combined with oxaliplatin could significantly inhibit the EMT process of gastric cancer. Poria cocos combined with oxaliplatin could significantly affect the morphology changes of gastric cancer cells. These findings may provide a theoretical guidance for the clinical treatment of gastric cancer.

BACKGROUND AND AIMS: In this study, we investigated the inhibitory effects of N-acetyl cysteine (NAC) on the growth of the human signet ring cell from the gastric-cancer cell line SJ-89 , via the induction of apoptosis and the arrest of DNA synthesis. MATERIALS AND METHODS: SJ-89 cells were regularly incubated in the presence of NAC at 5, 10 and 20 mmol/l, and with IMDM as untreated control. Trypan blue-dye exclusion analysis and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay were applied to detect cell proliferation. Apoptotic morphology was observed by electron microscopy. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay were performed to detect NAC-triggered apoptosis. RESULTS: NAC could inhibit proliferation of human gastric cancer SJ-89 cells in a dose-dependent and time-dependent manner. The growth curve showed suppression by 15.8, 37.6 and 66.3% following 72 h of NAC treatment at 5, 10 and 20 mmol/l, respectively, similar to the findings of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis was evidently reduced by 25, 39 and 91% after 24 h NAC treated at 20 mmol/l and 5 days at 10 and 20 mmol/l, respectively. Cell growth was inhibited by 100% with the treatment of 20 mmol/l NAC on day 6. NAC-treated SJ-89 cells were characterized by typical apoptotic alterations, including morphological changes by electron microscopy, typical apoptotic sub-G1 peaking observed by flow cytometry and increase of apoptotic cells with the elevation of the concentration of NAC in a clearly dose-dependent manner by TUNEL assay. Electrophoresis analysis showed typical 'DNA ladder'. CONCLUSION: The data above implicated that NAC inhibits human gastric-cancer SJ-89 cell growth by inducing apoptosis and DNA synthesis arrest. Although the exact mechanisms involved in NAC-induced apoptosis have not been known up to now, the ability to induce apoptosis in a tumor-cell population within 48 h is worth noting. It is also noteworthy that NAC can selectively inhibit the growth of tumor cells. Further studies are needed to elucidate the mechanisms.

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with <or=2 years follow-up (OR = 0.40, 95% CI = 0.19-0.83, P(trend) = 0.064). The inverse association was more pronounced in subjects consuming higher levels of red and processed meats, a factor that may increase endogenous N-nitroso compound production. The effect of plasma vitamin C was not different by GC anatomical subsite (cardia/non-cardia) or histological subtype (diffuse/intestinal), and there was no significant interaction of effect with H.pylori. The results of this study show, in a prospective setting, an inverse association of GC risk with high levels of plasma vitamin C and suggest an interaction with the intake of red and processed meats, whose consumption may elevate endogenous N-nitroso compound production.

OBJECTIVE: To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. METHODS: In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. RESULTS: After treatment with AA 3 mol/L + SS 2 mu mol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15 mu m.s-1.V-1.cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. CONCLUSION: These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

Background:Survival outcomes are still far from being satisfactory in patients with advanced gastric cancer, despite availability of novel chemotherapeutic regimens.

Aim:This study evaluated the outcomes of patients with advanced gastric cancer who received chemotherapy along with additional treatment modalities targeting multiple tumor cell vulnerabilities.

Materials and Methods:A total of 24 patients diagnosed with stage III-IV locally advanced or metastatic gastric adenocarcinoma that received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, local hyperthermia, and hyperbaric oxygen therapy (HBOT) between April 2014 and October 2017 were included in this retrospective study. Survival outcomes were evaluated.

Results:In 22 patients (88.0%), complete response was achieved. Mean duration of follow-up was 23.9± 12.7 months. Mean overall survival was 39.5 months (95% confidence interval [CI]: 28.1-51.0) and mean progression free survival was 36.5 months (95% CI: 25.7-47.2). No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or HBOT.

Conclusions:The combination treatment used in this study (MSCT together with a ketogenic diet, hyperthermia and HBOT) appears to be promising in the treatment of advanced gastric cancer. Further research and comparative clinical trials are warranted to support and standardize this novel treatment protocol.

It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway. It was demonstrated that the vitamin C-induced calcium influx and ROS generation have critical roles in the induction of apoptosis. Furthermore, vitamin C treatment depleted adenosine triphosphate (ATP) production in AGS cells, and the autophagy pathway may be involved in this process. Taken together, the current study suggests that a high dose of vitamin C may induce gastric cancer cell apoptosis through the dysfunction of mitochondria, including calcium influx, reactive oxygen species generation and ATP depletion.