Anti-gastric Cancer Activity Research Articles

Synthesis, crystal structure, and anti-gastric cancer activity of a heterometallic coordination polymer based on flexible 6,6′-dithiodinicotinic acid

A new bimetallic coordination polymer [In2Na(H2O)2(ddca)3](NO3)×4H2O (1, H2ddca = 6,6'-dithiodinicotinic acid) is produced via a hydrothermal reaction of In(NO3)3, H2ddca with NaOH as the pH modulator. Various characterization methods, such as thermogravimetric analysis (TGA), elemental analysis (EA), single crystal and powder X-ray diffraction measurements, are used. Furthermore, a process of sonochemistry with oleic acid at 453 K is used to produce nanoparticles of 1 (nano-1). In terms of the biological function of the synthesized complex, the real-time reverse transcription-polymerase chain reaction is carried out to explore the relative mRNA expression of miR-181 in MGC-803, BGC-823, and SGC-7901 gastric cancer cell lines, and the western blot is used to explore the protein expression of apoptotic protein Bcl-2.

Crystal structure and evaluation of the anti-gastric cancer activity of a new Sr(II)-based coordination polymer

In this study, a new Sr(II)-based coordination polymer containing Sr(II)-carboxyl chains with the formula [Sr3(L)2(H2O)2](H2O)3 is successfully prepared with the use of a non-planar tri­podal ligand 3,4-bi(4-carboxyphenyl)-benzoic acid (H3L) under the hydrothermal conditions. A single crystal X-ray diffraction study reveals that complex 1 has a three-dimensional framework with a 3-nodal (4,6,8)-connected topological net. Furthermore, an ultrasonic treatment method is used to produce the crystalline samples of 1 in the nanoscale (nano 1). The CKK-8 assay is performed to detect the cell proliferation of MGC-803 gastric cancer cells under the treatment with nano 1. Moreover, the cancer cell apoptosis is determined by a flow cytometer and the Western blot after treating with nano 1.

Crystal structures and anti-gastric cancer activities of two Cd(II)-based coordination polymers constructed from different donor ligands

Two new Cd(II)-containing coordination polymers, namely [Cd(H2O)2(L1)2](NO3)2 (1, L1 = 1,3-bis­(imidazol-1-yl)-5-methyl­benzene) and [Cd2(L2)(H2O)6](DMF)3 (2, H4L2 = 5,5'-(p-xylylenediamino)-1,1',3,3'-(benzene-tetra-carboxylic acid), are successfully prepared under the solvothermal conditions using different donor ligands. Complex 1 is a 2D layered structure whose network could be considered as a sql uninodal topological network, while complex 2 reveals a 3D supramolecular structure via H bond interactions between the adjacent 2D layers. Furthermore, the anticancer activity of the two complexes is studied via the CCK8 assay against the MGC-803 gastric cancer cell lines, which reveals that compound 1 exhibits a significantly stronger activity than compound 2.

Structural features and anti-gastric cancer activity of polysaccharides from stem, root, leaf and flower of cultivated Dendrobium huoshanense

The structure features and anti-gastric cancer activities in vitro of stem, root, leaf and flower polysaccharides from cultivated Dendrobium huoshanense were investigated systematically. Stem polysaccharide (cDHPS) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4)-3-O-acetyl-β-D-Manp-(1→ with the molecular weight of 2.59 × 105 Da; root polysaccharide (cDHPR) was composed of →3,5)-α-L-Araf-(1→, →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4,6)-β-D-Manp-(1→, →6)-α-D-Galp-(1→ and terminal β-L-Araf with the molecular weight of 1.41 × 104 Da; leaf polysaccharide (cDHPL) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4)-3-O-acetyl-β-D-Manp-(1→, →3,6)-β-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 2.09 × 105 Da; and flower polysaccharide (cDHPF) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →3,6)-β-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 4.78 × 105 Da. Among these four polysaccharides, cDHPS showed the best anti-gastric cancer activity evidenced by the inhibited growth and c-myc expression as well as the enhanced apoptosis and p53 expression of murine forestomach carcinoma (MFC) cells, suggesting their difference in anti-gastric cancer activity should be contributed to their difference in structure features.

Geranium thunbergii extract-induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells

ABSTRACT Geranium thunbergii is a traditional East Asian medicine for stomach diseases including dysentery and stomach ulcers in East Asia and has been reported to possess biological activity. The benefits of G. thunbergii in gastric cancer are unknown. In this study, we demonstrate that G. thunbergii extract suppresses proliferation and induces death and G1/S cell cycle arrest of gastric cancer cells. Proliferation was significantly inhibited in a time- and dose-dependent manner. Cell cycle arrest was associated with significant decreases in CDK4/cyclinD1 complex and CDK2/cyclinE complex genes expression. In addition, the protein expression of caspase-3 was decreased and that of activated poly (ADP-ribose) polymerase (PARP) was increased, which indicated apoptosis. The expressions of the Bax and Bcl-2, which are apoptosis related proteins, were upregulated and down-regulated, respectively. The results indicate that G. thunbergii extract can inhibit proliferation and induce both G/S cell cycle arrest and apoptosis of gastric cancer cells. Also, the induction of apoptosis involved the intrinsic pathways of the cells. Take the results, we suggest that G. thunbergii extract has anti-gastric cancer activity and may be a potential therapeutic candidate for gastric cancer.

RETRACTED: Synthesis, crystal structure, anti-gastric cancer activity of 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220954.

Design, synthesis, and anti-gastric cancer activity of novel 2,5-diketopiperazine

Over the past decades, anti-cancer drugs consist of cytotoxic drugs have been interested and developed. Despite the great advances in chemotherapy, there is still no certain medical treatment for cancer. During this investigation, a novel 2,5-diketopiperazine derivative 3(R),6(S)-bis (4-hydroxy phenyl)-piperazine-2,5-dione: (BHPPD) was designed, synthesized, and evaluated. The effects on intestinal protease consist of conformation, activity, and cytotoxic effect on cancer cell lines by the various methods were assessed. The binding interaction between BHPPD with α-Chymotrypsin (α-Chy) has been described utilizing many spectroscopic and computational approaches. Intrinsic fluorescence analyses exhibited static quenching as the primary quenching mod in α-Chy–BHPPD interaction, which is further confirmed by UV–vis analyses. Likewise, binding and thermodynamic constants are estimated from temperature dependent fluorescence results. Furthermore, structural alterations of the enzyme upon binding with BHPPD were presented by circular dichroism (CD) analyses. The Molecular docking assessment presented the specific binding microenvironment of BHPPD in α-Chy. Besides with this research, molecular dynamics Simulation is performed to estimate the stability of α-Chy, α-Chy–BHPPD system. These results showed the vigorous binding affinity of the drug with intestinal protease. MTT analysis of BHPPD represented high cytotoxic effect against AGS cell line compared to normal cell line. Quantitative analysis shows that BHPPD treatment significantly increased the expression of caspase3, 9, and 8 genes and decreased GR expression in AGS cell line. Our team hopes that the results of this research will be useful for medical science and pharmacy.

Synthesis and anti-gastric cancer activity evaluation of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties

A series of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties have been synthesized based on copper-catalyzed azide-alkyne cycloaddition (CuAAC). The anti-cancer activity of the new triazole nucleobase analogues was studied in gastric cancer cell lines (MGC-803, SGC-7901) and normal gastric epithelial cells (GES-1) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells. Among the tested compounds, compound 20c demonstrated good anti-proliferation activity against MGC-803 cells (IC50 = 1.48 μM) and SGC-7901 (IC50 = 2.28 μM) cells as well as the best selectivity between the cancer and normal cells. Further mechanistic studies indicated that compound 20c could down-regulate the expression of TGF β1 both in the tested gastric cancer cell lines and inhibit the cell migration and invasion. The results of the study indicate that compound 20c could be used as a promising skeleton for anti-gastric cancer agents with improved efficacy and less side effects.

RETRACTED ARTICLE: Synthesis, structure, and in vitro antigastric cancer activity evaluation of two new Zn(II) and Cd(II)-organic frameworks

We, the Editors and Publisher of the Journal of Coordination Chemistry, have retracted the following article: Zongnan Chen, Shupeng Zhang, Jianping Shao & Feng Su. Synthesis, structure, and in vitro antigastric cancer activity evaluation of two new Zn(II) and Cd(II)-organic frameworks, Journal of Coordination Chemistry; 2019, VOL. 72, NO. 11, 1833–1844. DOI: 10.1080/00958972.2019.1617416 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

RETRACTED: Synthesis, anti-gastric cancer activity and docking studies of naphthol derivatives

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220954.

Ketamine exhibits anti-gastric cancer activity via induction of apoptosis and attenuation of PI3K/Akt/mTOR.

IntroductionGastric cancer (GC) is the most widespread type of cancer after lung and liver cancer in men and after breast cancer in women. Thus, the present study was intended to evaluate the effect of ketamine (KET) on gastric cancer cells.Material and methodsThe effect of KET was analyzed in vitro by the MTT assay against human gastric cancer cell lines BGC-823, MKN-45 and MKN-28. The effect KET on apoptosis, cell migration and cell cycle arrest was also quantified. Western blot analysis was performed to estimate the effect of KET on apoptosis mediators and PI3K/AKT/mTOR pathway mediators. A mouse xenograft assay was also conducted to further confirm the anticancer activity.ResultsKET causes reduction of cellular viability of BGC-823, MKN-45 and MKN-28, with a more significant effect against BGC-823 cells. The KET treatment showed a dose-dependent increase in apoptotic cells among BGC-823 cells. KET causes a significant dose-dependent decline in migration of treated cells. It causes induction of apoptosis mediated via the mitochondrial pathway, where it causes a decline in Bcl2 and mitochondrial cytochrome c level together with increase in expression of Bax, cytosolic cytochrome c and cytosolic apoptotic protease activating factor-1 (Apaf-1). The level of p-PI3K, p-mTOR, p-GSK3β and p-AKT was found to be downregulated in a dose-dependent manner in KET-treated cells. In a mouse xenograft model, KET causes a reduction in relative tumour volume and tumour weight.ConclusionsOur results suggest that ketamine has the ability to inhibit progression of gastric cancer via induction of apoptosis and attenuation of PI3K/Akt/mTOR.

Synthesis, Structure and In Vitro Anti-gastric Cancer Activity of Two New Mixed-Ligand Cu(II) and Cd(II)-Coordination Polymers

By using a strategy of introducing two organic ligands with different donor groups, two new Cu(II) and Cd(II) coordination polymers (CPs) [Cu3(OH)(pz)3(Hpz)(H2O)(ipa)](H2O)4 (1, Hpz = pyrazol, H2ipa = isophthalic acid) and [Cd(phen)(ndc)](H2O) (2, phen = 1,10-phenanthroline, H2ndc = 1,2-naphthalene dicarboxylic acid) are synthesized and characterized. The molecular structures of the as-prepared CPs were determined by the single crystal X-ray diffraction (SCXRD) studies and their phase purities have been confirmed via the power X-day diffraction analysis (PXRD). The Cu(II)-based complex 1 is composed of trinuclear Cu3(µ3-OH)(pz)3 clusters that extended by the ipa2− ligands into a 1D left-handed helical chain along the c axis. In complex 2, the ndc2− ligands connect with the binuclear Cd2 unit along the c axis to shape a 1D chain-like structure, which is further stacked into a 2D layered network via π–π stacking. The as-prepared two CPs transformed to the nanoscale regime by mechanical grinding to yield nano 1 and nano 2 with excellent water dispersibility, maintaining its crystallinity. In addition, the in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were conducted on the gastric cancer cell line AGS with increasing concentrations of the two nanosized CPs, which reveal their promising anticancer activity.

RETRACTED ARTICLE: Bifunctional (3,6)-Connected Gd(III) Metal–Organic Framework Material with Catalytic Properties for the Cyanosilylation Reaction and Anti-gastric Cancer Activity

A new Gd(III) coordination polymer, namely [Gd(bpt)(H2O)(DMF)]n·3n(H2O) (1, H3bpt = biphenyl-3,4′,5-tricarboxylic acid, DMF = N,N-dimethylformamide), has been successfully synthesized under solvothermal conditions. In the structure of 1, the dinuclear [Gd2(COO)4] building subunits are connected by the bpt3− ligands into a 3D framework with (3,6)-connected flu-3,6-C2/c topology. Moreover, the catalytic performances of 1 and 1′ (desolvated sample) towards the cyanosilylation of benzaldehyde and its derivatives have been tested under mild conditions. The catalytic activity of 1′ is higher than that of compound 1, indicating that more open metal sites in coordination polymer is beneficial to the cyanosilylation reaction. In addition, in vitro anticancer activities of compounds 1 and 1′ (desolvated sample) on four human gastric cancer cells (MGC-803, SGC-790, MKN45 and AGS) were further determined.

A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents.

Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.

In Vitro antigastric cancer activity of squalene, a triterpenoid compound isolated from Rhizophora Mucronata mangrove plant leaves against AGS cell line

Background: Mangrove plants have high potential in medical research and they have been used in traditional medicine for any diseases. Squalene, a natural 30-carbon triterpenoid compound, was originally obtained from Shark and for the first time isolated from mangrove plant species. From the historical background, it was known that squalene display protective actions against several diseases and carcinogens. Objective: Herein, we desire to report the in vitro evaluation of squalene on AGS cell line. In the present investigation, after 24 h incubation, the inhibitory effect of squalene was found to have significant activity on AGS cell lines proliferation. Materials and Methods: Mangrove plant isolated squalene compound was treated with gastric adenocarcinoma cancer cell line AGS for 24 h with control. The cells were treated at varying concentration range 10, 30, and 50 μg/mL. The cytotoxicity effect of squalene was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide, mitochondria membrane potential, etc., Results: Among the tested concentrations, squalene at 50 μg/mL showed a higher level of mitochondrial depolarization, DNA fragmentation, and induced apoptosis in AGS cells when compared to control. A similar but lower activity was observed in minimum doses of 20 and 30 μg/mL compared to maximum dose of 50 μg/mL. A 50% and 100% cell viability was observed at 30 and 50 μg/mL, respectively. Likewise, there was a significant reduction in thiobarbituric acid reactive substrate and lipid hydroperoxides levels, while antioxidant enzymes like superoxide dismutase. Catalase, glutathione (GSH) peroxidase, reduced GSH, Vitamin-C (Vit-C), and Vitamin-E were increased on squalene treatment in a dose-dependent manner. Conclusion: On the basis of results, it was concluded that isolated compound (squalene) from Rhizophora mucronata had a potent antigastric carcinogenic effect at 50 μg/mL in AGS cell lines and appeared to be more sensitive toward the AGS cell line. Abbreviations used: PBS: Phosphate-buffered saline; FBS: Fetal bovine serum; DMEM: Dulbecco's modified eagle medium; MTT: 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-tetrazolium bromide; DCFH-DH-7: Diacetyl dichlorofluorescein; Rh 123: Rhodamine 123; EB: Ethidium bromide; AO: Acridine orange; TBA: Thiobarbituric acid; NBT: Nitro blue tetrazolium; PMS: Phenazine methosulfate; DTNB-5: 5-dithiobis 2-nitrobenzoic acid; GSH: Reduced glutathione.

Industrial Applications of Selected JFS Articles

Industrial Applications of Selected <i>JFS</i> Articles

Antigastric Cancer Bioactive Aurantiochytrium Oil Rich in Docosahexaenoic Acid: From Media Optimization to Cancer Cells Cytotoxicity Assessment.

Thraustochytrid microbial oil rich in DHA, showed antigastric cancer activity comparable to that of pure DHA; indicating that this microbial bioactive omega-3 oil rich in the very important PUFA (DHA), can be applied as an additive for the fortification of food and dairy products. Also, Aurantiochytrium sp. KR091914, as a GRAS microorganism, is a good producer of this bioactive oil.

Enhancing the anti-gastric cancer activity of curcumin with biocompatible and pH sensitive PMMA-AA/ZnO nanoparticles

Curcumin loaded ZnO nanoparticles were successfully synthesised and encapsulated with co-polymer PMMA-AA (Cur/PMMA-AA/ZnO NPs). The ZnO nanoparticles have been converted as good cargo materials to carry the well-known hydrophobic drug curcumin by surface functionalization. Physical characteristics of these novel nanomaterials have been studied with transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) in conjunction with spectral techniques. A narrow particle size distribution with an average value of 42nm was found via TEM. Most importantly, the pH-responsive release of curcumin from the nano-vehicle ensures safer, more controlled delivery of the drug at physiological pH. The drug entrapment efficiency and loading was evaluated and the in vitro efficacy as anticancer drug delivery vehicle was analyzed. The potential toxicity of Cur/PMMA-AA/ZnO NPs was studied by using AGS gastric cancer cell lines via MTT assay. These results revealed that the proposed nanomaterials induce a remarkable cell death in in-vitro models. The multifunctional properties of Cur/PMMA-AA/ZnO NPs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy.

Garlic-derived organosulfur compound exerts antitumor efficacy via activation of MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice

Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested for its antigastric cancer activities in various preliminary studies. However, more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly needed. The aim of this study was to investigate the antitumor effects of DATS in the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo using widely recommended study procedures. DATS suppressed cancer cells proliferation and induced cell cycle arrest accompanied by an increase in the expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused an increase in apoptotic cell death, which involved in accumulations of bax, p53, and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK, ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen-activated protein kinase (MAPKs) pathways were involved in DATS-induced apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein expressions. In addition, DATS treatment evidently increased the cytokine secretions of IL-12, TNF-α and IFN-γ (p<0.05). Biochemical serum analysis and histopathological examination indicated no obvious side effects in major mouse organs. Therefore, our findings provide a framework for further exploration of DATS as a novel chemotherapeutic for human gastric cancer.

The Antigastric Cancer Activity of San Leng Powder Extract Induces Apoptosis in Balb/C Bearing-SGC-7901 Mice.

San Leng powder extract has been used as medicinal compound for the prevention and treatment of cancers. The antitumor activity of SLPE was determined by treating BALB/C mice harboring a human gastric cancer xenograft with SPLE for 17 days. Mice were also treated with fluorouracil (5-Fu, 25 mg/kg) or a combination of SLPE and 5-Fu. Our results indicate that the inhibition of tumor growth by SLPE might be due to a block in the cell cycle and the induction of apoptosis. These results suggest that SLPE might be useful in the treatment of gastric cancer.