Human Gastric Adenocarcinoma Cells Research Articles

Eudesmin attenuates Helicobacter pylori-induced epithelial autophagy and apoptosis and leads to eradication of H. pylori infection.

Eudesmin has been proven to possess anti-inflammatory effects. In the present study, the effects of eudesmin on Helicobacter pylori (H. pylori)-mediated autophagy, apoptosis, immune response and inflammation were determined in human gastric adenocarcinoma (AGS) cells in vitro and in C57BL/6 mice in vivo. Detection of the production of interleukin (IL)-8, IL-1β and immunoglobulin M (IgM) was performed using ELISA. Identification of the activation of apoptosis-associated caspase-3, −8 and −9 proteins, Bcl-2-associated X protein (Bax) and BH3 interacting domain death agonist (Bid) protein, was determined through western blot analysis. Autophagy microtubule-associated protein 1A/1B-light chain 3, isoform B (LC-3B) expression was measured using immunostaining. The results of the present study demonstrated that eudesmin inhibited the growth of H. pylori, with increased inhibition activity against antibiotic resistant strains compared with the reference strain. In addition, H. pylori-induced IL-8 secretion, LC-3B expression and apoptosis-associated protein (caspase-3, −8 and −9, Bax and Bid) activation in AGS cells was suppressed by eudesmin. Furthermore, eudesmin suppressed IL-1β and IgM production in H. pylori-infected C57BL/6 mice in vivo. In conclusion, eudesmin may be developed as a promising therapeutic agent to prevent and/or treat H. pylori-associated gastric inflammation.

Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells.

During gastric cancer (GC) progression, increased extracellular matrix (ECM) deposition, notably collagen type I, correlates with an overall increase in expression of the mesenchymal phenotype. In GC tissue, the intestinal epithelium exhibits impaired cell-cell adhesion and enhanced cell-ECM adhesion. The alteration of intercellular integrity is one of tumorigenesis feature including tumor invasion and metastasis. Using a density-varying ECM, we studied the effect of ECM density on both intercellular- and ECM-interactions according to alterations of ECM-mediated signaling. A dense collagen matrix increases integrin-mediated cell-ECM interactions with phosphorylated FAK and ERK signaling in human gastric adenocarcinoma cells (AGS, MKN74), which regulates GC proliferation and the chemotherapeutic response. In addition, GC cells exhibited a disrupted membranous E-cadherin/β-catenin complex and, remarkably, showed cytoplasmic or nucleic localization of β-catenin in response to collagen density. Furthermore, we found that membranous E-cadherin/β-catenin complex could be recovered by inhibiting the phosphorylation of FAK, which in turn influences the chemotherapeutic effect. These results provide insight into how matrix density differentially regulates cancer cell phenotype and may have significant implications for the design of biomaterials with appropriate physical properties for in vitro tumor models.

FOXO3 Inhibits Human Gastric Adenocarcinoma (AGS) Cell Growth by Promoting Autophagy in an Acidic Microenvironment

Background/Aims: Previous studies have shown that FOXO3, a member of the forkhead box O (FOXO) family, regulates autophagy in various cells. To date, whether the induction of autophagy in gastric cancer (GC) cells is triggered by an acidic microenvironment is unclear. Little is known about the relationship between FOXO3 and acidic microenvironments in GC. The aims of our study were to investigate the roles of FOXO3 and the acidic microenvironment in autophagy and to determine how FOXO3 and the acidic microenvironment regulate GC cell growth through autophagy. Methods: We cultured human gastric adenocarcinoma (AGS) cells in media with different pH values in vitro, transfected the cells with FOXO3a plasmids and then detected autophagy in the cells under different conditions. In addition, we also performed cell counting kit 8 (CCK8), wound and cell invasion assays to test cell viability and invasion, respectively. We employed real-time PCR, western blotting and mRFP-GFP-LC3 vectors to detect the expression of various autophagy indicators. Results: We found that cells treated with FOXO3 and exposed to an acidic microenvironment displayed suppressed growth compared with control cells. We also found that the protein expression levels of several autophagy makers, such as LC3I, LC3II and Beclin-1, were higher in FOXO3 plasmid-transfected AGS cells cultured in an acidic microenvironment than in control cells, while P62 protein expression levels were clearly decreased in FOXO3 plasmid-transfected cells compared with control cells. Moreover, we observed autophagic flux in AGS cells overexpressing FOXO3 and exposed to low pH conditions. Conclusion: These findings suggest that FOXO3 inhibits AGS cell growth by promoting autophagy in an acidic microenvironment. Furthermore, the results showed that anticancer therapies targeting FOXO3 and low pH conditions may be useful in the treatment of GC.

The Signaling pathways involved in Fluoxetine-induced apoptosis in human gastric adenocarcinoma cell line (AGS)

The Signaling pathways involved in Fluoxetine-induced apoptosis in human gastric adenocarcinoma cell line (AGS)

Celastrus orbiculatus extracts induce apoptosis and inhibit invasion by targeting the maspin gene in human gastric adenocarcinoma cells.

Celastrus orbiculatus Thunb. has been used as a remedy against cancer and inflammatory diseases for thousands of years in China. Maspin is expressed in normal cells and downregulated in prostate tumor cells. The underlying mechanisms between C. orbiculatus extract (COE) and maspin remain unclear. In the present study, 3 target-specific 19–25 nucleotide maspin small interfering RNAs were designed and synthesized to knockdown maspin expression. The effects of COE on MGC-803/maspin− cell proliferation were evaluated by the MTT assay. Apoptosis was measured by flow cytometry. Invasive activity was measured with the Transwell assay and the associated molecular mechanisms were assessed by western blot analysis. The results demonstrated that COE significantly promoted the expression of maspin (P<0.01) to induce apoptosis and inhibit invasion and migration in MGC803 cells. The expression levels of phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK), phospho-extracellular regulated protein kinase (Erk), B cell lymphoma-2-associated X protein and caspase-3 were increased in the MGC-803/maspin− cells in a dose-dependent manner. The Erk, B-cell lymphoma 2, p-Akt, Akt and p-mechanistic target of rapamycin (mTOR) protein in MGC-803/maspin− cells were reduced in a dose-dependent manner. This indicated that COE may inhibit invasion and migration through phosphoinositide 3-kinase/Akt/mTOR and MAPK signaling pathways in MGC-803/maspin− cells. In conclusion, COE has the ability to improve the expression of maspin to induce apoptosis and inhibit invasion and migration in human gastric adenocarcinoma cells.

Changes in polyphenol composition and bioactivity of the native Chilean white strawberry (Fragaria chiloensis spp. chiloensis f. chiloensis) after in vitro gastrointestinal digestion

The Chilean white strawberry (Fragaria chiloensis spp. chiloensis f. chiloensis) is a semi-domesticated strawberry with high polyphenol content and antioxidant activity occurring in southern Chile. The aim of this work was to compare the composition and bioactivity of the polyphenol-enriched fruit extract (PEE) before and after simulated gastrointestinal digestion (GID). Results show a decrease by >50% in the total phenolic (TP) content at the end of the GID, compared to the non-digested PEE. A reduction in the antioxidant capacity of the PEEs was observed after GID by means of DPPH, FRAP, TEAC and anion superoxide assays. After simulated GID the PEE significantly inhibited α-glucosidase with an IC50 value of 3.13μg/mL. The inhibition of pancreatic lipase was reduced by 95% after GID. All the PEEs did not show inhibitory effect towards α-amylase throughout the GID. In the same way, the PEEs did not significantly protect human gastric adenocarcinoma (AGS) cells against H2O2-induced stress. Thirty eight compounds were tentatively identified in the non-digested PEE. The compounds that were more affected by the simulated GID were simple phenolics. After the GID, only 33 and 25 compounds were detected, in the gastric and intestinal steps, respectively. These results evidence the changes elicited by GID on the bioactivity and polyphenolic composition of the white strawberry.

Cerenkov luminescence imaging on evaluation of early response to chemotherapy of drug-resistant gastric cancer

Apoptosis imaging enables a timely and specific assessment of treatment response in cancer patients. In this study, we applied a probe for positron emission tomography (PET), which served as an optical biomaterial emitting Cerenkov photons, to in vivo optical imaging of tumor apoptosis, in order to evaluate early response to chemotherapy of drug-resistant gastric cancer. 68Ga-DOTA-Annexin V was prepared as the apoptosis targeting probe. Wild type human gastric adenocarcinoma cell line SGC7901/WT and drug vincristine-resistant variant SGC7901/VCR were used to establish normal and vincristine-resistant xenografts to simulate treatment decision situation. Vincristine-resistance of SGC7901/VCR and apoptosis-induction ability of vincristine and cisplatin were verified. In vitro and in vivo CLI of apoptosis was performed. Stronger signals of apoptosis of CLI correlated with confirmed higher levels of apoptosis and subsequent changes in tumor sizes. Our study suggests that CLI is a promising technique for in vivo imaging of apoptosis with radiopharmaceutical-labeled biomaterials.

Outer inflammatory protein a (OipA) of Helicobacter pylori is regulated by host cell contact and mediates CagA translocation and interleukin-8 response only in the presence of a functional cag pathogenicity island type IV secretion system.

OipA is a phase-variable virulence factor of Helicobacter pylori. Mutations in oipA to turn the gene phase on in a cag pathogenicity island (PAI)-negative strain of H. pylori (J68) or phase off in a cag PAI-positive strain (26695) demonstrated that phase on oipA alleles in both strains had both increased oipA mRNA and human gastric adenocarcinoma (AGS) cell adherence compared to isogenic oipA phase off mutants. An oipA phase off mutant of H. pylori 26695 demonstrated decreased IL-8 secretion by AGS cells and failure to translocate the cag PAI effector CagA. Increased attachment by OipA expressing cag PAI-negative H. pylori J68 failed to alter secreted IL-8 levels. Thus, OipA is necessary but not sufficient for the induction of IL-8; however, it is necessary for translocation of the oncoprotein CagA. Perhaps the nearly invariant phase on status of oipA alleles among cag PAI-positive H. pylori isolates relates to the role of this outer membrane protein in effective translocation of CagA. oipA mRNA comparisons between AGS cell-adherent and non-adherent H. pylori 26695 revealed significantly greater levels in the adherent cells. This may allow H. pylori to adapt to conditions of host cell contact by altering expression of this virulence factor.

Abstract A05: Derivation of chemotherapeutic combination against gastric cancer cells via synthetic lethal targeting of conserved drug-resistance network in fission yeast surrogate

Abstract Cancer is a global health problem and there is a critical need for new advancements in its management and treatment if we are to meet the projected increase in new cases. One important challenge facing clinicians is how to determine the most appropriate treatment strategy for patients. Thus far, chemotherapy has remained the mainstay for cancer management. Contemporary chemotherapeutic treatments incorporate the use of typically three to four agents in combination. The determination of the most suitable drug combination profoundly affects chemotherapeutic success. However, selecting the most appropriate drugs for such therapy is not necessarily a straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our approach employed the single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells using a synthetic lethality workflow. Using a group of genes that we have uncovered to confer responsiveness towards the topoisomerase II inhibitor doxorubicin, a widely applied therapeutic agent in a wide range of cancers. We assessed the genetic overlap of the doxorubicin responsive network with that of several other chemotherapeutic agents harboring varied mechanisms of action. From these effort, we have determined a synergistic combination between three chemotherapeutic agents that include the intrastrand crosslinking agent cisplatin, histone deacetylase inhibitor suberoylanilide acid (SAHA) with doxorubicin. Interestingly, our results revealed that SAHA and doxorubicin affect the integrity of the chromatin at the centromeric core domain to undermine chromosome segregation fidelity. On the other hand, we and others have reported that doxorubicin and cisplatin result in DNA damage in fission yeast cells and dependent upon homologous recombination machinery for proper repair. These results suggest that the mechanism of action of the combined effect of these drugs is mediated via induction of genomic instability following imprecise mitotic chromosome segregation and the damaging of DNA. We further showed that the drug combination can inflict apoptotic cell death in human gastric adenocarcinoma cells, which exhibited cleavage of caspases and the poly ADP ribose polymerase upon drug treatment. The cells also displayed changes in epigenetic modifications that included the upregulation of phosphorylation of histone H2AX, which is a marker for DNA damage, as well as global alteration in histone acetylation level, latter mainly due to the treatment with SAHA. Concomitantly, activities of several cell signalling kinases were altered in the gastric adenocarcinoma cells upon drug treatment indicative of the pathway specificity that relayed the damage signals in response to the drugs. Taken together our findings point to the usefulness of fission yeast as a model in revealing in screening for successful chemotherapeutic drug combinations for human cells via differential targeting of a conserved gene interaction network. Citation Format: Eesin-. Chen, Kwishan-. Seah, Thuytrang-. Nguyen. Derivation of chemotherapeutic combination against gastric cancer cells via synthetic lethal targeting of conserved drug-resistance network in fission yeast surrogate [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr A05.

MiR-101-3p Suppresses HOX Transcript Antisense RNA (HOTAIR)-Induced Proliferation and Invasion Through Directly Targeting SRF in Gastric Carcinoma Cells.

miR-101-3p has been identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all six human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS, and HGC-27. Overexpression of miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells, and knockdown of miR-101-3p displayed the opposite effect. In addition, miR-101-3p could directly target and suppress the expression of the serum response factor (SRF) gene, which is a transcription factor of HOTAIR, a well-characterized tumor promoter lncRNA. miR-101-3p negatively regulated SRF-mediated transcription of HOTAIR. Moreover, silencing of either SRF or HOTAIR could counteract the promotion of gastric adenocarcinoma cell proliferation and invasion by miR-101-3p inhibition. Our findings indicate that miR-101-3p suppresses HOTAIR-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells.

Further insights on tomato plant: Cytotoxic and antioxidant activity of leaf extracts in human gastric cells

This study focused the toxicity against human gastric adenocarcinoma cells (AGS) and the antioxidant activity of hydromethanol (HME), acetone (AcE) and alkaloid (AE) extracts prepared from the leaves of tomato plant cultivars (Caramba, Valentine, Negro, Abuela, and Anairis). AE, HME and AcE extracts of all cultivars reduced cell viability, IC50 values ranging from 9 ± 2 to 55 ± 11, from 103 ± 25 to 171 ± 29 and from 291 ± 26 to 459 ± 14 μg mL−1, respectively. Moreover, both HME and AcE extracts scavenged •NO (IC50 values ranged from 0.87 ± 0.12 to 1.54 ± 0.23 and from 0.90 ± 0.01 to 2.23 ± 0.14 mg mL−1, respectively), but only HMEs was able to scavenge O2•- showing IC50 values from 0.12 ± ≤0.01 to 0.43 ± 0.08 mg mL−1. Our results demonstrate that tomato leaves, a by-product of tomato processing industry, are a valuable source of bioactive compounds, providing beneficial properties for human health.

Ethnopharmacological use of Cymbopogon citratus (DC.) Stapf and Cymbopogon schoenanthus (L.) Spreng.: Anti-inflammatory potential of phenol-rich extracts

Aim: The aim of this work consisted on expanding the knowledge on the chemical composition of different extracts from Cymbopogon spp., and on the evaluation of their anti-inflammatory potential in cell and cell-free systems. Introduction: The ethnopharmacological use of Cymbopogon spp. dates back from ancient times. Traditionally used in tropical and semi-tropical countries for the repellent properties of their essential oil, the consumption of Cymbopogon spp. infusions is growing all over the world. This is not only due to the unique aroma, widely appreciated by the consumers, but also because of the antimicrobial, anti-inflammatory and sedative properties.1 Methods: The chemical characterization of infusions and ethanol:water (50:50, v/v) extracts from Cymbopogon citratus and Cymbopogon schoenanthus was achieved by HPLC-DAD. The anti-inflammatory potential of the extracts was assessed by cell and cell-free assays. Results: HPLC-DAD analysis allowed the identification of several caffeic acid derivatives and flavonoids in the infusions and in the ethanol:water extracts of both species. The different extracts displayed scavenging activity against superoxide anion and nitric oxide (NO) radicals, and capacity to significantly reduce NO production by LPS-stimulated macrophages (RAW 264.7 cell line). In addition, the extracts were able to prevent hyaluronic acid degradation via inhibition of hyaluronidase, an enzyme recognized to participate in a number of physiological and pathological processes, including inflammation.2 No toxicity was observed on human gastric adenocarcinoma and hepatocyte carcinoma cell lines, at a maximum concentration of 2.0mg lyophilised extract/mL. Conclusion: This study provided scientific evidence on the ethnopharmacological use of Cymbopogon species on inflammatory conditions, encouraging infusion consumption and future incorporation of Cymbopogon spp. extracts into nutraceuticals. Acknowledgements: This work received financial support from National Funds (FCT/MEC) through project UID/QUI/50006/2013, co-financed by FEDER through COMPETE, under the Partnership Agreement PT2020, and from NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through ERDF (NORTE-01-0145-FEDER-000024). MB is indebted to FCT for the grant (SFRH/BD/95861/2013).

Germacranolides from Enhydra fluctuans with TRAIL-resistance Abrogating Activity

TRAIL selectively kills cancer cells without harming most normal cells. However, TRAIL resistance is a major problem for its therapeutic use. Developing a strategy to overcome resistance is crucial for the successful use of TRAIL as an antitumor agent. In our screening program of natural products that can abrogate TRAIL resistance, four germacranolides (1–4) were isolated from the aerial parts of Enhydra fluctuans. All compounds exhibited potent TRAIL-resistance overcoming activity against TRAIL-resistant human gastric adenocarcinoma (AGS) cells.

The Cytotoxic Effects of Eggplant Peel Extract on Human Gastric Adenocarcinoma Cells and Normal Cells

The Cytotoxic Effects of Eggplant Peel Extract on Human Gastric Adenocarcinoma Cells and Normal Cells

Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer.

Celastrus orbiculatus is a traditional medicinal plant used in the anti-inflammatory and analgesic treatment of various diseases. A previous study demonstrated that ethyl acetate extract of C. orbiculatus (COE) exhibited significant antitumor effects. However, studies concerning the effects and mechanism of COE in terms of suppressing the epithelial-mesenchymal transition (EMT) in human gastric adenocarcinoma cells have not been performed at present. The present study hypothesized that COE may inhibit EMT in gastric adenocarcinoma cells by regulating cell cytoskeleton rearrangement. The effect of COE on the viability of AGS cells was detected by MTT assay. An EMT model was induced by transforming growth factor-β1. Cell cytoskeleton staining, laser scanning confocal microscopy and electronic microscopy were used to detect the changes in cell morphology and microstructure of gastric adenocarcinoma cells prior and subsequent to COE treatment. Invasion and migration assays were used to observe the effect of COE on the metastatic ability of AGS cells in vitro. The effect of COE on the expression of Cofilin 1 and EMT biomarkers, including Epithelial-cadherin, Neural-cadherin, Vimentin and matrix metalloproteinases, was examined by western blotting in AGS cells. The correlation between Cofilin 1 and EMT was investigated with immunofluorescence and cytoskeleton staining methods. The results demonstrated that COE may significantly inhibit the process of EMT in AGS cells, and that this was concentration-dependent. In addition, COE significantly downregulated the level of Cofilin 1 in a concentration-dependent manner. In conclusion, these results suggested that Cofilin 1 was directly involved in the process of EMT in AGS cells, and that it served an important function. COE may significantly inhibit EMT in AGS cells, potentially by inhibiting the activation of the Cofilin 1 signaling pathway. The present study may provide a basis for the development of novel anticancer drugs and the development of novel therapeutic strategies, targeting Cofilin 1 protein.

Effects of natural phenolic compound carvacrol on the human gastric adenocarcinoma (AGS) cells in vitro.

Gastric cancer (GC) is the most common cause of morbidity and mortality because of cancer. Medicinal plants containing polyphenolic compounds have gained importance in anticancer treatment. In this context, carvacrol is a main component of many plants in the family Lamiaceae that are frequently used in folk medicine and a good candidate to investigate for GC treatment. The present study aimed to explore the cytotoxic, genotoxic, apoptotic, and reactive oxygen species (ROS)-generating effects of carvacrol on gastric adenocarcinoma in vitro. For these purposes, human gastric adenocarcinoma (AGS) cells were used and analyzed after 24 h of exposure to carvacrol with different concentrations. The cytotoxicity, ROS generation, glutathione (GSH) level, and genotoxicity were investigated by the ATP cell viability assay, 2',7'-dichlorodihydrofluorescein-diacetate assay, GSH/GSSG-Glo assay, and comet assay, respectively. Apoptosis induction was detected by acridine orange/ethidium bromide staining and western blotting at below the half-maximal growth inhibitory concentration value. Carvacrol showed cytotoxic, genotoxic, apoptotic, ROS generating, and GSH-reducing effects on AGS cells in a dose-dependent manner. There was a close negative relationship between cell viability and ROS level. Carvacrol inhibited the proliferation of AGS cells, suggesting that it could be a novel and strong anticancer agent against the human gastric adenocarcinoma. These results support the interest of natural diet components in the development of therapeutic products for diseases.

Effects of miR-21 on proliferation and apoptosis in human gastric adenocarcinoma cells.

The present study investigated the expression of miR-21 in MGC803 gastric cancer cells and its effects on Bcl-2 expression and cell proliferation, apoptosis, and invasion. In total 50 patients were recruited with gastric cancer who were admitted to the Henan Province People's Hospital. The samples of gastric cancer and the adjacent normal tissues were collected after surgery. We found that mRNA levels of miR-21 and Bcl-2 were significantly elevated in tumor tissues compared to control tissue. The expression of Bcl-2 protein was also elevated in cancerous tissue. This high expression of Bcl-2 was associated with clinical stage, lymph node metastasis, and tumor differentiation degree. Inhibition of miR-21 reduced the levels of miR-21 and Bcl-2 in MGC803 cells, and lowered cell proliferation and invasiveness. These results indicate that miR-21 and Bcl-2 may participate in the occurrence and development of gastric adenocarcinoma, suggesting their potential role as biomarkers and therapeutic targets.

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis.

Direct and efficient intracellular delivery of enzymes to cytosol holds tremendous therapeutic potential while remaining an unmet technical challenge. Herein, an ultrasound (US)-propelled nanomotor approach and a high-pH-responsive delivery strategy are reported to overcome this challenge using caspase-3 (CASP-3) as a model enzyme. Consisting of a gold nanowire (AuNW) motor with a pH-responsive polymer coating, in which the CASP-3 is loaded, the resulting nanomotor protects the enzyme from release and deactivation prior to reaching an intracellular environment. However, upon entering a cell and exposure to the higher intracellular pH, the polymer coating is dissolved, thereby directly releasing the active CASP-3 enzyme to the cytosol and causing rapid cell apoptosis. In vitro studies using gastric cancer cells as a model cell line demonstrate that such a motion-based active delivery approach leads to remarkably high apoptosis efficiency within a significantly shorter time and with a lower amount of CASP-3 compared to other control groups not involving US-propelled nanomotors. For instance, the reported nanomotor system can achieve 80% apoptosis of human gastric adenocarcinoma cells within only 5 min, which dramatically outperforms other CASP-3 delivery approaches. These results indicate that the US-propelled nanomotors may act as a powerful vehicle for cytosolic delivery of active therapeutic proteins, which would offer an attractive means to enhance the current landscape of intracellular protein delivery and therapy. While CASP-3 is selected as a model protein in this study, the same nanomotor approach can be readily applied to a variety of different therapeutic proteins.

Sharkquinone, a new ana-quinonoid tetracene derivative from marine-derived Streptomyces sp. EGY1 with TRAIL resistance-overcoming activity.

A new ana-quinonoid tetracene metabolite, named sharkquinone (1), and the known SS-228R (2) have been isolated from the ethyl acetate extract of the culture of marine Streptomyces sp. EGY1. The strain was isolated from sediment sample collected from the Red Sea coast of Egypt. The structure of sharkquinone (1) was elucidated using detailed spectral (HRESI-MS, 1D and 2D NMR) analyses and quantum chemical calculations. This is the first report of the isolation of ana-quinonoid tetracene derivative from a natural source. Compound 1 showed the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance at a concentration of 10μM in human gastric adenocarcinoma (AGS) cells.

Flavone polyphenols dominate in Thymus schimperi Ronniger : LC–ESI–MS/MS characterization and study of anti-proliferative effects of plant extract on AGS and HepG2 cancer cells

Thymus schimperi is a highly localized and a rare plant endemic to Ethiopia. An optimized and validated high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was applied to characterize 23 polyphenolic compounds found in ethyl acetate extracts of the plant. From those, flavones dominated and luteolin was the major component contributing 21.83% of the total composition (or 46.05±0.59g/kg of fresh sample weight). Validation data showed a determination coefficient (R2)≥0.997. Limits of detection (LOD) and quantification (LOQ) were 0.03-0.97 and 0.11-3.23mg/L, while recovery values spiked at 5 and 50mg/L were between 70.89-115.39 and 67.65-120.19%, respectively. Except for caffeic acid and epicatechin gallate, the relative standard deviations (%RSDs) were far below 15%, showing acceptable precision values. The plant extracts inhibited cell proliferation and induced cell death in human gastric adenocarcinoma (AGS) and liver hepatocellular carcinoma (HepG2) cancer cells. This is the first report of polyphenolic components from T. schimperi being characterized using HPLC-ESI-MS/MS. Being components of many edible vegetables, fruits, and spices, the identified polyphenols suggest that T. schimperi could be a potential food with promising health benefits.