• DNA damage
• DNA damage responses
• ROS
• Synthetic lethality

• Acacetin
• Antibiotic resistance
• Apoptosis
• Gastric epithelial GES-1 cells
• Helicobacter pylori
• Infection

• anticancer properties
• apoptosis
• cancer management
• molecular mechanisms
• phenethyl isothiocyanate
• signaling pathways

• Isothiocyanates/pharmacology
• Humans
• Neoplasms/drug therapy
• Animals
• Apoptosis/drug effects
• Signal Transduction/drug effects
• Cell Proliferation/drug effects
• Antineoplastic Agents/pharmacology
• NF-kappa B/metabolism
• Antineoplastic Agents, Phytogenic/pharmacology

• apoptosis
• bioinformatics analysis
• cell cycle
• gastric cancer
• lycopene

• cancer
• in vivo study
• lycopene
• nutraceuticals

Antibiotic-resistant Helicobacter pylori isolates have become a global concern. The standard triple or quadruple therapies have recently become the most effective protocol for eradicating H. pylori in the gastrointestinal tract. There is evidence regarding the impact of different complementary or dietary supplements on H. pylori eradication. This review article intended to search electronic bibliographic databases for any clinical studies that evaluated the use of any herbal or dietary supplements to eradicate H. pylori up to June 2021. A total of 20 human studies met our criteria and were reviewed. Although some herbal medicines have shown their efficacy and safety in eradicating H. pylori in different clinical trials, more randomized blind, placebo-controlled human trials with a large sample size must be performed to extend our knowledge.

• Cancer
• Combretastatin
• Eribulin
• Ginsenoside
• Mycobacterium bovis
• Novel molecules
• Plitidepsin

• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents, Phytogenic/therapeutic use
• Aquatic Organisms
• Bacteria
• Biological Products/therapeutic use
• Humans
• Neoplasms/drug therapy

• Cell apoptosis
• DNA damage response
• Luteolin
• MAPK/IκBα/NF-κB
• Network pharmacology
• Oxidative stress

• H. pylori
• clinical treatment
• diet
• infection
• nutrition

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study. The general and pathological evaluation, gastric secretion, as well as the levels of antioxidant and inflammatory factors were detected. In lycopene experimental groups, the amount of gastric juice were lower than that in the gastric injury control group; the levels of T-SOD, and the levels of MDA and inflammatory factors (MMP-9 and MCP-1) decreased. However, general and pathological evaluation of gastric tissues revealed that lycopene (especially at high doses) could aggravate acute gastric mucosal injury induced by ethanol. Therefore, lycopene (especially at high doses) aggravates acute gastric mucosal injury caused by ethanol, but this was not due to oxidative stress or inflammatory factors. In lycopene control group, the levels of MTL, T-SOD, and NO increased, but the levels of ALT and AST decreased, indicating that lycopene has a protective effect on the stomach and liver when ethanol wasn't taken. It reminds us that, when alcohol is consumed in large quantities, consumption of lycopene products should be carefully considered.

• acute gastric injury
• antioxidant
• ethanol
• liver
• lycopene

• Cancer
• Delivery systems
• Lycopene
• Molecular mechanisms
• Synergy

• Animals
• Anticarcinogenic Agents
• Drug Delivery Systems
• Humans
• Lycopene
• Neoplasms

• DNA repair activators
• aging
• antioxidants
• epidrugs
• genomic protection
• geroprotectors
• senolytics
• senomorphics

• Aging
• Animals
• Genome/drug effects
• Genomic Instability
• Humans
• Pharmaceutical Preparations/administration & dosage
• Protective Agents/therapeutic use

• 19-74-00083 Russian Science Foundation
• АААА-А18-118011120004-5 Ministry of Science and Higher Education of the Russian Federation

Helicobacter pylori (H. pylori) infection leads to the massive apoptosis of the gastric epithelial cells, causing gastric ulcers, gastritis, and gastric adenocarcinoma. Autophagy is a cellular recycling process that plays important roles in cell death decisions and can protect cells by preventing apoptosis. Upon the induction of autophagy, the level of the autophagy substrate p62 is reduced and the autophagy-related ratio of microtubule-associated proteins 1A/1B light chain 3B (LC3B)-II/LC3B-I is heightened. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are involved in the regulation of autophagy. Astaxanthin (AST) is a potent anti-oxidant that plays anti-inflammatory and anti-cancer roles in various cells. In the present study, we examined whether AST inhibits H. pylori-induced apoptosis through AMPK-mediated autophagy in the human gastric epithelial cell line AGS (adenocarcinoma gastric) in vitro. In this study, H. pylori induced apoptosis. Compound C, an AMPK inhibitor, enhanced the H. pylori-induced apoptosis of AGS cells. In contrast, metformin, an AMPK activator, suppressed H. pylori-induced apoptosis, showing that AMPK activation inhibits H. pylori-induced apoptosis. AST inhibited H. pylori-induced apoptosis by increasing the phosphorylation of AMPK and decreasing the phosphorylation of RAC-alpha serine/threonine-protein kinase (Akt) and mTOR in H. pylori-stimulated cells. The number of LC3B puncta in H. pylori-stimulated cells increased with AST. These results suggest that AST suppresses the H. pylori-induced apoptosis of AGS cells by inducing autophagy through the activation of AMPK and the downregulation of its downstream target, mTOR. In conclusion, AST may inhibit gastric diseases associated with H. pylori infection by increasing autophagy through the activation of the AMPK pathway.

• AMP-activated protein kinase
• Helicobacter pylori
• apoptosis
• astaxanthin
• autophagy

• AMP-Activated Protein Kinases/genetics
• AMP-Activated Protein Kinases/metabolism
• Anti-Inflammatory Agents
• Antineoplastic Agents
• Antioxidants
• Apoptosis/drug effects
• Apoptosis/genetics
• Autophagy/drug effects
• Autophagy/genetics
• Cell Line, Tumor
• Epithelial Cells/microbiology
• Epithelial Cells/physiology
• Gastric Mucosa/cytology
• Gastritis/microbiology
• Gastritis/physiopathology
• Helicobacter Infections
• Helicobacter pylori
• Humans
• Microtubule-Associated Proteins/genetics
• Microtubule-Associated Proteins/metabolism
• Phosphorylation/drug effects
• Signal Transduction/drug effects
• Signal Transduction/genetics
• TOR Serine-Threonine Kinases/genetics
• TOR Serine-Threonine Kinases/metabolism
• Xanthophylls/pharmacology

Helicobacter pylori infection causes chronic gastritis and is the major risk factor of gastric cancer. H. pylori induces a chronic inflammation-producing reactive oxygen species (ROS) which is a source of chromosome instabilities and contributes to the development of malignancy. H. pylori also promotes DNA hypermethylation, known to dysregulate essential genes that maintain genetic stability. The maintenance of telomere length by telomerase is essential for chromosome integrity. Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase activity and an important target during host-pathogen interaction. We aimed to investigate the consequences of H. pylori on the regulation of TERT gene expression and telomerase activity. In vitro, hTERT mRNA levels and telomerase activity were analysed in H. pylori-infected human gastric epithelial cells. In addition, C57BL/6 and INS-GAS mice were used to investigate the influence of H. pylori-induced inflammation on TERT levels. Our data demonstrated that, in vitro, H. pylori inhibits TERT gene expression and decreases the telomerase activity. The exposure of cells to lycopene, an antioxidant compound, restores TERT levels in infected cells, indicating that ROS are implicated in this downregulation. In vivo, fewer TERT-positive cells are observed in gastric tissues of infected mice compared to uninfected, more predominantly in the vicinity of large aggregates of lymphocytes, suggesting an inflammation-mediated regulation. Furthermore, H. pylori appears to downregulate TERT gene expression through DNA hypermethylation as shown by the restoration of TERT transcript levels in cells treated with 5′-azacytidine, an inhibitor of DNA methylation. This was confirmed in infected mice, by PCR-methylation assay of the TERT gene promoter. Our data unraveled a novel way for H. pylori to promote genome instabilities through the inhibition of TERT levels and telomerase activity. This mechanism could play an important role in the early steps of gastric carcinogenesis.

• Helicobacter pylori
• epigenetic
• gastric cancer
• methylation
• miRNAs

• Carcinogenesis/genetics
• Cell Transformation, Neoplastic/genetics
• Epigenesis, Genetic/genetics
• Helicobacter Infections/complications
• Helicobacter pylori/genetics
• Humans
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

• Helicobacter pylori
• DNA damage
• NF-κB
• PLK

Reactive oxygen species (ROS) contribute to the oncogenic phenotype of cancer cells by acting as signaling molecules for inducing proliferation. ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs) pathway. The Ras-dependent pathway promotes the activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB), a transcriptional modulator of cyclooxygenase-2 (COX-2) that induces cell proliferation. Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables. This study aims to investigate whether lycopene inhibits proliferation and induces apoptosis in gastric cancer AGS cells by suppressing the EGFR/Ras/MAPK and NF-κB-COX-2 signaling axis. Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio). Lycopene reduced the level of intracellular and mitochondrial ROS and decreased the activation of the ROS-mediated EGFR/Ras/extracellular signal-regulated kinase (ERK) and p38 MAPK pathways, thus leading to attenuation of the DNA-binding activity of NF-κB p50/p50 and the level of COX-2 gene expression. These results show that lycopene-induced apoptosis and inhibition of proliferation occur via inhibition of ROS-activated EGFR/Ras/ERK and p38 MAPK pathways and NF-κB-mediated COX-2 gene expression in AGS cells. In conclusion, consumption of lycopene-enriched foods could decrease the incidence of gastric cancer.

• apoptosis
• cyclooxygenase-2
• epidermal growth factor receptor
• gastric cancer
• lycopene

• DNA repair
• Genomic instability
• Helicobacter pylori
• Oxidative stress
• Stem cells

Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori–induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori–infected gastric epithelial cells.

We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori–infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined.

H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori–infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori–infected gastric epithelial cells, similar to KRG.

KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori–infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• Apoptosis
• Gastric epithelial cells
• Helicobacter pylori
• Panax ginseng

• Helicobacter pylori
• Jak1
• Lycopene
• Stat3
• Wnt
• β-Catenin

• Cell Proliferation
• Cyclin E/metabolism
• Diet
• Epithelial Cells/drug effects
• Epithelial Cells/metabolism
• Epithelial Cells/pathology
• Gastric Mucosa/drug effects
• Gastric Mucosa/metabolism
• Gastric Mucosa/microbiology
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter Infections/prevention & control
• Helicobacter pylori/growth & development
• Humans
• Janus Kinase 1/metabolism
• Lycopene/pharmacology
• Lycopene/therapeutic use
• NF-kappa B/metabolism
• Oncogene Proteins/metabolism
• Oncogenes
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Proto-Oncogene Proteins c-myc/metabolism
• Reactive Oxygen Species/metabolism
• STAT3 Transcription Factor/metabolism
• Stomach/cytology
• Stomach/drug effects
• Stomach/microbiology
• Stomach/pathology
• Vegetables/chemistry
• Wnt Proteins/metabolism
• beta Catenin/metabolism

The increased resistance of Helicobacter pylori to antibiotics has increased the need to develop new treatments for this bacterium. The aim of our study was to identify new drugs with anti-H. pylori activity.

We screened a small molecule library—the library of pharmacologically active compounds (LOPAC), which includes 1,280 pharmacologically active compounds—to identify inhibitors of H. pylori growth. The minimal inhibitory concentrations (MICs) of antibiotics against multidrug-resistant H. pylori strains were determined using the agar dilution method.

We identified diphenyleneiodonium (DPI) as a novel anti-H. pylori agent. The MIC values for DPI were <0.03 μg/mL against all tested H. pylori strains. DPI also exhibited strong antibacterial activity against common gram-negative and gram-positive pathogenic bacteria.

DPI may be a candidate anti-H. pylori drug for future development.

• Anti-bacterial agents
• Diphenyleneiodonium
• Drug resistance, multiple
• Helicobacter pylori
• Minimal inhibitory concentration

• Acetylcysteine/pharmacology
• Acetylcysteine/therapeutic use
• Animals
• DNA Damage/physiology
• Helicobacter Infections/drug therapy
• Helicobacter pylori/drug effects
• Humans
• Male
• Mice
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Reactive Oxygen Species/metabolism

• Lycopene
• antioxidant
• health effects

Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.

• Rose hip
• antimicrobial
• antioxidants
• arthritis
• cancer
• diabetes
• functional food
• neural disorder
• oxidative stress

• Animals
• Antioxidants/chemistry
• Antioxidants/pharmacology
• Antioxidants/therapeutic use
• Dietary Supplements
• Humans
• Medicine, Traditional/methods
• Oxidative Stress/drug effects
• Phytochemicals
• Plant Extracts/chemistry
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Plants, Medicinal/chemistry
• Rosa/chemistry
• Solubility

• Glutamine
• Hydrogen peroxide
• Interleukin-8
• Janus kinase
• Signal transducers of activated transcription

Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies.

• Anticancer effect
• Gastric carcinogenesis
• Lycopene

• Helicobacter pylori
• NADPH oxidase
• apoptosis
• diphenyleneiodonium
• gastric epithelial cells

• Apoptosis
• Apoptosis Regulatory Proteins/metabolism
• Cell Survival
• Epithelial Cells/metabolism
• Epithelial Cells/microbiology
• Gastric Mucosa/metabolism
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/drug effects
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Humans
• NADPH Oxidases/metabolism
• Onium Compounds/antagonists & inhibitors
• Onium Compounds/pharmacology
• Oxidative Stress/drug effects
• Reactive Oxygen Species/metabolism
• Republic of Korea
• Stomach/cytology
• Stomach/microbiology

• angiogenesis
• apoptosis
• cycle arrest
• survival pathways
• β-phenethyl isothiocyanate

• Animals
• Anticarcinogenic Agents/pharmacology
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Cycle/drug effects
• Cell Line, Tumor
• Endoplasmic Reticulum Stress/drug effects
• Humans
• Isothiocyanates/pharmacology
• Male
• Mitochondria/drug effects
• NF-kappa B
• Signal Transduction/drug effects

AIM: To explore the relationship between the change of reactive oxygen species (ROS) and DNA damage caused by Helicobacter pylori (H. pylori) infection in gastric epithelial cells.

METHODS: H. pylori ACTC43504 (CagA⁺, VacA⁺) infected GES-1 cells were used in this study. Live cell imaging system was used to observe the change of intracellular ROS, and a microplate reader was used to detect intracellular ROS level. Single cell gel electrophoresis comet assay was used to detect DNA damage.

RESULTS: ROS level was proportional to H. pylori concentration, and the ROS level was the highest when the MOI of H. pylori was 300:1. Various concentrations of N-acety-L-cysteine (NAC) could significantly inhibit the generation of ROS caused by H. pylori infection. H. pylori could cause DNA damage. After NAC pretreatment, the values of tail length, comet length, tail moment, and Olive tail moment had a clear downward trend compared with the H. pylori group.

CONCLUSION: H. pylori infection in GES-1 cells increases intracellular ROS level and results in DNA damage. Inhibition of the generation of ROS could reduce DNA damage.

• Helicobacter pylori
• GES-1 cells
• ROS
• DNA damage

Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori-) infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA), a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation), levels of reactive oxygen species (ROS), NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits), activation of redox-sensitive transcription factors (NF-κB, AP-1), expression of oncogenes (β-catenin, c-myc), and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.

• Carotenes
• Chronic diseases
• NF-κB
• Nrf2
• Transcription factors
• Xanthophylls

• Gastric epithelial cells
• Helicobacter pylori
• MCP-1
• Panax ginseng C.A. Meyer
• Red ginseng extract (RGE)
• iNOS

• Cell Line
• Chemokine CCL2/antagonists & inhibitors
• Chemokine CCL2/genetics
• Epithelial Cells/drug effects
• Epithelial Cells/metabolism
• Gastric Mucosa/cytology
• Helicobacter Infections/metabolism
• Helicobacter pylori
• Humans
• Janus Kinase 2/metabolism
• NADPH Oxidases/metabolism
• Nitric Oxide Synthase Type II/antagonists & inhibitors
• Nitric Oxide Synthase Type II/genetics
• Panax
• Plant Extracts/pharmacology
• Reactive Oxygen Species/metabolism
• STAT3 Transcription Factor/metabolism

Phosphorylation of H2AX at Ser 139 (γH2AX) is a biomarker of DNA double-strand breaks (DSBs). The present study aimed to explore the association between γH2AX levels and gastric pathology and Helicobacter pylori (H. pylori) infection. Gastric biopsies were obtained from 302 H. pylori-negative and -positive patients, including those with chronic gastritis (CG), intestinal metaplasia (IM), dysplasia (Dys) and gastric cancer (GC). Proteins were extracted from five gastric epithelial cell lines and from 10 specimens of matched GC and adjacent normal tissues. The expression of γH2AX, a biomarker for the detection of DNA DSBs, in gastric tissues was detected by immunohistochemistry and western blotting. The expression of γH2AX progressively increased in tissues according to pathological stage from CG to Dys, but was slightly decreased in GC. H. pylori infection was associated with increased γH2AX expression, IM and Dys. Overexpression of γH2AX in GC was found to correlate with tumor location, gross appearance, differentiation, depth of invasion, TNM stage and lymph node metastasis. The results indicated that DSBs appear to be an early molecular event in gastric carcinogenesis, which may be associated with H. pylori infection. Moreover, immunohistochemical staining of γH2AX was found to correlate with a number of clinicopathological characteristics. The expression of γH2AX may serve as a valuable biomarker for the diagnosis and progression of GC.

• DNA double-strand breaks
• Helicobacter pylori
• gastric carcinogenesis
• γH2AX

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents/therapeutic use
• Cell Line, Tumor
• DNA/metabolism
• DNA Breaks, Double-Stranded
• Female
• Gastric Mucosa/metabolism
• Helicobacter Infections/drug therapy
• Helicobacter Infections/metabolism
• Helicobacter pylori/drug effects
• Helicobacter pylori/pathogenicity
• Histones/genetics
• Histones/metabolism
• Humans
• Immunohistochemistry
• Intracellular Signaling Peptides and Proteins/genetics
• Intracellular Signaling Peptides and Proteins/metabolism
• Male
• Middle Aged
• Peptic Ulcer/genetics
• Peptic Ulcer/pathology
• Tumor Suppressor p53-Binding Protein 1