Apoptosis Of MGC-803 Cells Research Articles

WASF3 Knockdown Sensitizes Gastric Cancer Cells to Oxaliplatin by Inhibiting ATG12-Mediated Autophagy

BackgroundGastric cancer is one of the most aggressive tumors, usually resulting in metastasis, and therapies for advanced gastric cancer remain limited. Drug resistance is the main reason for chemotherapeutic failure in gastric cancer. Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis of different cancers. However, there has been little study of WASF3 expression involvement in gastric cancer. In this study, we explored the role of WASF3 in the sensitivity of gastric cancer to oxaliplatin, and the underlying mechanisms. MethodsWe silenced WASF3 using WASF3-siRNA in MGC803 cells. Then, CCK-8, flow cytometry and transwell assay were performed to study the effect of WASF3 silencing on proliferation, migration, invasiveness and apoptosis of MGC803 cells. Moreover, we evaluated the potential mechanism in vitro to determine the sensitization to oxaliplatin induced by WASF3. ResultsWASF3 silencing by small interfering RNA inhibited the proliferation, migration and invasiveness of gastric cancer cells. We also observed that WASF3 knockdown promoted cell apoptosis and enhanced oxaliplatin sensitivity. Furthermore, the sensitization to oxaliplatin induced by WASF3 knockdown depended on the inhibition of Atg12-mediated autophagy. ConclusionsOur analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.

Effects of Huaier Polysaccharide SP1 on Gastric Cancer Cell Proliferation, Apoptosis, Migration, and Invasion by Regulating TGF-β/SMAD Signaling Pathway

Objective. To study the effects of Huaier polysaccharide SP1 on the proliferation, apoptosis, migration, and invasion of gastric cancer cell line MGC-803 and the underlying mechanism. Methods. MGC-803 cells were cultured in vitro and treated with SP1. The effects of SP1 on the proliferation, apoptosis, migration, and invasion of MGC-803 cells were detected by CCK-8 assay, flow cytometry analysis, and Transwell assay, respectively. Western blot and qRT-PCR were used to detect the expression of related genes. Results. Our study showed that Huaier polysaccharide SP1 could inhibit proliferation, migration, invasion, and promote the apoptosis of MGC-803 cells in vitro in a dose-dependent manner. Huaier polysaccharide SP1 could inhibit the activation of TGF-β/SMAD signal pathway by upregulating SMAD7 expression, thereby downregulating the expression of SOX4, ZEB2, MMP9, Snail, and Slug. Conclusion. Huaier polysaccharide SP1 can regulate the proliferation, apoptosis, migration, and invasion of gastric cancer cells by promoting the expression of SMAD7 and inhibiting the activation of TGF-β/SMAD signal pathway as well as the expression of the downstream oncogenes.

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.

Antiproliferative Evaluation In Vitro of a New Chalcone Inducing Apoptosis by ROS Generation Against MGC-803 Cells

We have evaluated the antiproliferative activity of (E)-3-(3,5-difluorophenyl)-1-(2,4,6-trimethoxyphenyl)- prop-2-en-1-one (chalcone 5) against MGC-803 cells. This chalcone analog displayed a potent antiproliferative activity with an IC50 value of 0.23 μM against MGC-803 cells. It could induce apoptosis and regulate the apoptosis-related markers (Bax, Bcl-2, Bcl-xl, and Bid) in a concentration dependent manner. Treatment with NAC almost completely attenuated chalcone-induced cell inhibition and cell apoptosis in MGC-803 cells, indicating that the apoptotic mechanisms were related to ROS generation. Therefore, this chalcone derivative is a new apoptosis inducer for prevention and treatment of gastric cancer.

MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis.

Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma.

Synthesis and biological evaluation of vanadium complexes as novel anti-tumor agents

A class of vanadium complexes were prepared and investigated for their antiproliferative effects by MTT assay. The structure-activity relationship was extensively studied through the ligand variation. The results showed that the synthetic vanadium complexes demonstrated moderate to good antiproliferative activities against the four cancer cell lines including MGC803, EC109, MCF7 and HepG2, respectively. Of note was that most of the complexes showed preferential growth inhibitory activity to some degree toward gastric cancer line MGC803. Among them, complex 19 exhibited the most and broad-spectrum proliferative inhibition against the tested cell lines. In addition, mechanism studies illustrated that complex 19 could prevent the colony formation, migration and EMT process, as well as induce apoptosis of MGC803 cells. Furthermore, Western blot experiments revealed that the expression of apoptosis-related proteins changed, including up-regulation of Bax, PARP and caspase-3/9, as well as down-regulation of Bcl-2.

Discovery of the theobromine derivative MQS-14 that induces death of MGC-803 cells mainly through ROS-mediated mechanisms

Reactive oxygen species (ROS) play crucial roles in maintaining redox balance and regulating physiological processes, ROS levels in cancer cells are relatively higher than those in normal cells. Therefore, elevating cellular ROS levels may be a viable strategy for selective killing of cancer cells. In this work, we synthesized a series of new theobromine derivatives and evaluated their cytotoxicity against gastric cancer cells MGC-803, SGC-7901 and HGC-27. Particularly, MQS-14 potently inhibited cell growth of MGC-803, SGC-7901 and HGC-27 cells at low micromolar levels. Mechanistic studies showed that compound MQS-14 decreased cell viability of MGC-803 cells and inhibited cell division revealed by the CFDA and EdU staining assays. MQS-14 increased cellular ROS levels and activated the MAPK pathway accompanied by the decreased p-ERK and increased p-JNK expression. MQS-14 also induced DNA damage and apoptosis in MGC-803 cells. To conclude, MQS-14 induced cell death of MGC-803 cells partly through elevating cellular ROS levels.

Abamectin induces apoptosis and autophagy by inhibiting reactive oxygen species-mediated PI3K/AKT signaling in MGC803 cells.

Abamectin (ABA) is one of the most widely used compounds in agriculture and veterinary medicine. However, the cytotoxicity of ABA in human gastric cells is utterly unknown. In this study, ABA suppressed the proliferation of MGC803 cells by arresting the cell cycle at the G0/G1-phase. Moreover, ABA induced mitochondrial-mediated apoptosis by inducingthe loss of mitochondrial membrane potential, upregulationof Bax/Bcl-2, and activation of caspase-3. ABA significantly improved the LC3-II/LC3-I ratio and reduced P62 protein expression in a dose-dependent manner. Through detection of the reactive oxygen species (ROS) levels, we found ABA induced the accumulation of intracellular ROS and then reduced PI3K/AKT signaling activation relatedto MGC803 cellapoptosis and autophagy. Our results indicate that ABA exerts cytotoxic effects on human MGC803 cells through apoptosis and autophagy by inhibiting ROS-mediated PI3K/AKT signaling. Furthermore, ABA may be a potential risk to human gastric health.

Design, synthesis, and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and suppress cell migration

Amino acid derivatives containing chrysin were synthesized for evaluating their anticancer effects. Among them, compound N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)heptanoyl)-L-isoleucine (6e) displayed the most potent antiproliferative activity against MGC-803 cells with IC50 value of 20.0 μM. Preliminary mechanistic studies showed that compound 6e could inhibit the colony formation and migration of MGC-803 cells. Flow cytometry analysis demonstrated that compound 6e mediated cell apoptosis of MGC-803 cells and arrested cell cycle in G2/M-phase. Moreover, 6e treatment in MGC-803 cells downregulated anti-apoptotic protein Bcl-2 and upregulated pro-apoptotic gene Bax in a concentration-dependent manner. Our studies suggest that compound 6e may sever as an effective chemotherapeutic candidate.

Effects of silkworm pupa protein hydrolysates on mitochondrial substructure and metabolism in gastric cancer cells

Abstract The effects of silkworm pupa protein hydrolysates (SPPHs) on the apoptosis of MGC-803 gastric cancer cells were investigated in this study. The role of mitochondrial-dependent apoptosis in SPPHs-dependent inhibition of MGC-803 cell viability was also explored. SPPHs were found to induce apoptosis in MGC-803 cells with an IC50 of 0.30 mg/ml. A series of changes in cellular organelle structural were observed during MGC-803 cell apoptosis that included mitochondrial swelling, vacuolation and rupture. These changes may ultimately impact on metabolic energy supply in MGC-803 cells. The expression of the pro- and anti-apoptotic proteins Bcl-2 and Bax, and the activation of cytochrome c (Cyt C), Caspase-3 and Caspase-9 were altered following induction of apoptosis by SPPHs in MGC-803 cells. Moreover, the increase in the ratio of Bax to Bcl-2 expression is known to play an important role in the activation of the mitochondrial-dependent apoptotic pathway.

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents.

A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3'-C5' positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.

Novel 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives as potent anti-gastric cancer agents: Design, synthesis and structural optimization

To explore anti-gastric cancer agents with high efficacy and selectivity, we report the design, synthesis and optimization of a novel series of 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives starting from the compound PCA-15 reported by us previously. Most of the target compounds demonstrated significant antiproliferative effects on MGC803 cancer cell line, and more potent than the positive control (PCA-15 and 5-Fu). Among them, compound 6o was identified to be the most active compound against MGC803 cell line with an IC50 value of 0.84 μM. Additionally, high selectivity was also observed between cancer and normal cells (23.35 μM against GES-1). Further mechanism studies confirmed that compound 6o could inhibit colony formation and migration, induce the apoptosis of MGC803 cells through both the mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which were evidenced by the up-regulation of Bax, cleaved-caspase 9/3/8, cleaved PARP and down-regulation of Bcl-2. Our systematic studies implied a new scaffold targeting gastric cancer cells for further development of small-molecule compounds with improved potency and selectivity.

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties.

Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, 1H-NMR, 13C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound 4j exhibited promising cytotoxicity with IC50 values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC50 > 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound 4j was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore, 4j may be further exploited as a novel pharmacophore model for the development of anticancer agents.

DS2, a newly synthetic ent-kaurane diterpenoid analog, inhibits proliferation and migration of human gastric cancer cell

Objective: To investigate the effects and the underlying mechanism of DS2, a newly synthetic analog of natural ent-kaurane diterpenoid, on the proliferation and migration capabilities of human gastric cancer cells. Methods: MTT assay, colony formation assay and flow cytometry were used to measure the effects of DS2 on growth, apoptosis and cell cycle of several human gastric cancer cell lines. The function of DS2 in the migration was further detected by wound healing and transwell assays. The expression of migration related proteins were determined by western blot. Results: DS2 inhibited the growth of MGC-803, SGC-7901 and HGC-27 cells in a dose dependent manner. After treatment of DS2 at a concentration of 6.25 μmol/L for 24 h, the survival rates of MGC-803, SGC-7901 and HGC-27 cells were 53.87±3.05%, 55.91±6.97% and 32.41±2.64%, respectively. However, for the normal gastric epithelial cell GES-1, no obvious growth inhibition was observed. In addition, DS2 caused significant G(2)/M arrest and induced apoptosis in MGC-803 cells. Furthermore, compared with the negative control, the colony formation, wound healing rate as well as the number of migrating cells of MGC-803 were significantly decreased in a dose dependent manner after DS2 treatment. DS2 induced the expression of E-cadherin, whereas β-catenin and N-cadherin levels were downregulated in MGC-803. Conclusion: The new compound DS2 has a strong anti-cancer activity, and this study will help us to design and synthesize better diterpenoids derivatives.

Syntheses, Crystal Structures, and Antitumor Activities of Copper(II) and Nickel(II) Complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol.

Two transition metal complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (L), [Cu(L)Cl2]2 (1) and [Ni(L)Cl2]·CH2Cl2 (2), were synthesized and fully characterized. Complex 1 exhibited high in vitro antitumor activity against SK-OV-3, MGC80-3 and HeLa cells with IC50 values of 3.69 ± 0.16, 2.60 ± 0.17, and 3.62 ± 0.12 μM, respectively. In addition, complex 1 caused cell arrest in the S phase, which led to the down-regulation of Cdc25 A, Cyclin B, Cyclin A, and CDK2, and the up-regulation of p27, p21, and p53 proteins in MGC80-3 cells. Complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway, as shown by the significantly decreased level of bcl-2 protein and the loss of Δψ, as well as increased levels of reactive oxygen species (ROS), intracellular Ca2+, cytochrome C, apaf-1, caspase-3, and caspase-9 proteins in MGC80-3 cells.

Swertia mussotii extracts induce mitochondria-dependent apoptosis in gastric cancer cells

Swertia mussotii (Gentianaceae) is a traditional Chinese medicinal plant grown in the Qinghai-Tibet Plateau. Three fractions from S. mussotii extract, named SWF50, SWF 70 and SWF100, were screened for in vitro anti-proliferative activity on two gastric cancer cell lines, MGC-803 and BGC-823 cells using MTT assay. Our results demonstrated that SMF70 showed an anti-proliferative effect in MGC-803 cells and SMF100 showed an anti-proliferative effect in BGC-823 cells in vitro. Moreover, both two fractions induced apoptosis via depolymerization of cytoskeletal filaments, increased cytoplasmic levels of ROS and Ca2+ and disrupted mitochondrial transmembrane potential. In addition, flow cytometry analysis indicated that both two fractions could induce cell apoptosis and arrest the cell cycle at S phase. Our results indicate that SMF70 induces apoptosis of MGC-803 cells and SMF100 induces apoptosis of BGC-823 cells via a mitochondrial-dependent pathway. Meanwhile, we also investigated antitumor effect of SMF70 in vivo, and exhibited effective tumor growth inhibition. Our findings demonstrate that S. mussotii extracts could be a potential new alternative therapeutic agent gastric cancer.

Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway.

B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to examine the effects of B7-H4 on the tumorigenicity of gastric cancer cells and to elucidate the underlying mechanisms. For this purpose, B7-H4 expression in gastric cancer tissues was detected by immunohistochemical staining. The effects of B7-H4 on the biological behavior of the MGC-803 human gastric cancer cell line were examined by Cell Counting kit-8 (CCK-8) assay, cell cycle analysis, wound healing assay, AnnexinV/propidium iodide staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Moreover, the expression levels of apoptotic markers, such as cleaved caspase‑3, cleaved caspase‑9, Bcl-2 and Bax were examined by western blot analysis. Immunohistochemical staining revealed that a high expression of B7-H4 was found in about 41.8% of tissues obtained from patients with gastric cancer. Comparative analysis revealed that B7-H4 expression significantly correlated with lymph node metastasis and the TNM stage. The results of CCK-8 assay, cell cycle analysis, wound healing assay, AnnexinV/propidium iodide staining assay and TUNEL assay all demonstrated that the silencing of B7-H4 by small interfering RNA decreased cell proliferation, suppressed cell motility, and induced cell cycle arrest and the apoptosis of MGC-803 human gastric cancer cells. Furthermore, the results of western blot analysis indicated that the downregulation of B7-H4 induced the apoptosis of the MGC-803 cells via the mitochondrial signaling pathway through the activation of caspase‑3 and caspase‑9, and by altering the Bax/Bcl-2 ratio in a manner that favored apoptosis. Based on the findings on human gastric cancer cell line MGC-803, the findings of this study suggested that B7-H4 may have the potential to be a valuable prognostic marker and a target for individualized therapies for gastric cancer. However, further investigations are required in order to confirm our findings on a larger scale.

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

Gastric cancer is considered as a common malignancy with a poor prognosis as well as unsatisfactory treatment. Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to affect multiple aspects of human tumor, including gastric cancer. This study aims to explore the effects of NGAL gene silencing on the proliferation as well as apoptosis of human gastric cancer MGC-803 cells. This study included 87 patients with gastric cancer. MGC-803 cells were collected and mainly treated with siRNA against NGAL and recombinant NGAL plasmid. The expression of NGAL mRNA and the expressions of NGAL protein and apoptosis-related proteins were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Cell cycle and apoptosis were tested by flow cytometry, and cell proliferation was detected by water soluble tetrazolium-1 (WST-1) assay. The effect of NGAL gene silencing on tumorigenicity of MGC-803 cells in vivo was detected through establishment of xenograft in nude mice. NGAL was highly expressed in gastric cancer tissues. The protein and mRNA expressions of NGAL gene in MGC-803 cells treated with NGAL-siRNA were obviously reduced, and the amount of cells in G0/G1 phase was increased. Moreover, MGC-803 cells treated with NGAL-siRNA exhibited inhibited proliferation, enhanced apoptosis, decreased expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) as well as B-cell lymphoma-2 (Bcl-2) and increased expressions of cysteine-aspartic acid specific protease-9 (caspase-9) and Bcl2-associated X (Bax), as well as repressed tumorigenicity in vivo. NGAL gene silencing inhibits proliferation and promotes apoptosis of MGC-803 cells, which can provide a novel theory for treatment of gastric cancer.

Design, synthesis and preliminary biological evaluation of 5,8-dihydropteridine-6,7-diones that induce apoptosis and suppress cell migration

Pteridines are an important class of fused heterocycles found in natural products and drug molecules, and have shown diverse biological activities. A focused library of 5,8-dihydropteridine-6,7-dione derivatives were designed and evaluated for their antiproliferative activity against MGC-803, SGC-7901, A549 and PC-3 cancer cell lines. The SARs studies highlighted the importance of the piperazine substituted 5,8-dihydropteridine-6,7-dione frameworks for the activity and revealed essential structural elements. Among these compounds, compound 5n displayed the most potent and broad-spectrum antiproliferative inhibition against the tested cell lines and was sensitive to MGC-803 cell line, slightly more potent than 5-FU. Preliminary mechanistic studies showed that compound 5n could inhibit the colony formation and migration of MGC-803 cells. Besides, flow cytometry analysis showed that compound 5n concentration-dependently induced apoptosis of MGC-803 cells. Our studies suggest that the piperazine substituted 5,8-dihydropteridine-6,7-dione frameworks may be regarded as new chemotypes for designing effective antitumor agents targeting gastric cancer cells.

Curcumol inhibits the proliferation of gastric adenocarcinoma MGC-803 cells via downregulation of IDH1.

Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric(GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the AnnexinV/propidium iodide(PI) staining followed by fluorescence activated cell sorting(FACS) analysis demonstrated that the cell cycle was arrested in the G2/Mphase by curcumol. AnnexinV-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species(ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase1(IDH1) was observed in the MGC-803cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.