Human Gastric Adenocarcinoma Cell Line Research Articles

Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells

AimsAnti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches. Thus, the need of integrative and comparative studies still persists. Materials and methodsIn this study we tested and compared the effects of three different cannabinoid receptor agonists-anandamide (AEA), (R)-(+)-methanandamide (Meth-AEA) and CP 55,940 (CP)- on gastric cancer cell morphology, viability and death events in order to provide new insights to the use of these agents for therapeutic purposes. Key findingsThe three agents tested exhibited similar concentration-dependent effects in the induction of changes in cell morphology and cell loss, as well as in the decrease of cell viability and DNA laddering in the human gastric adenocarcinoma cell line (AGS). Differences among the cannabinoids tested were mostly observed in the density of cells found in early and late apoptosis and necrosis, favoring AEA and CP as the more effective inducers of apoptotic mechanisms, and Meth-AEA as a more effective inducer of necrosis through transient and rapid apoptosis. SignificanceThrough a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.

Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response.

Interferon-λ1 (IFN-λ1), a recently discovered cytokine of the typeIII IFN family, was found to be a therapeutic alternative to typeI IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN‑λ1 recombinant adenovirus (rL-hIFN-λ1) containing human IFN-λ1 gene and further evaluated the expressing of IFN-λ1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-λ1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-λl specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs.The expression of the IFN-λ1 proteins reached a high level detected in the supernatant harvested 24h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-λ1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-λ1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and AnnexinV flow cytometry. Due to the high dose of IFN-λ1 expressed by the rL-hIFN-λ1-infected tumor cells, the immune study showed that rL-hIFN-λ1 increased IFN-γ production [the Thelper cell subtype1 (Th1) response] and inhibited interleukin(IL)-13 production [the Thelper cell subtype2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-λ1 as an efficient antitumor agent.

Effects of combining erlotinib and RNA-interfered downregulation of focal adhesion kinase expression on gastric cancer.

ObjectiveTo investigate the synergistic effects of combining erlotinib and RNA-interference downregulation of focal adhesion kinase (FAK) expression on the proliferation, apoptosis, invasion and migration of the human gastric adenocarcinoma cell line AGS.MethodsCells were divided into five experimental groups: Group A, nontransfected control; Group B, transfected with empty vector; Group C, transfected with FAK-shRNA; Group D, erlotinib treatment; Group E, combination erlotinib treatment and transfected with FAK-shRNA. FAK protein levels were confirmed via Western blotting. Cell proliferation (CCK-8 assay, apoptosis (flow cytometry), cell invasion (transwell assay) and migration (scratch assay) were evaluated.ResultsRNA interference significantly decreased FAK protein levels. Cell proliferation, invasion and migration were significantly lower in Groups C, D and E compared with Group A, and significantly lower in Group E than in Groups C and D.ConclusionsRNA interference effectively silences FAK expression and inhibits malignant cell proliferation and invasion in gastric cancer cells. The effect of FAK inhibition is increased by co-treatment with erlotinib.

Immunomodulatory Effects of Psyllium Extract on Helicobacter pylori Interaction With Gastric Epithelial Cells.

Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.

Curcumin Effect on the Expressional Profile of OCT4, Nanog and Nucleostemin Genes in AGS (Adenocarcinoma) Cancer Cell Line

Background: Curcumin is the natural yellow pigment in turmeric isolated from the rhizome of the plant Curcuma longa. Curcumin inhibits formation and invasive cancer cells and destroys cancer cells resistant to chemotherapeutic drugs. Objectives: The purpose of this study was the survey of effects of different concentrations of alcoholic curcumin on the octamer-binding transcription factor 4 (OCT4) Nanog and Nucleostemin genes in the AGS (human gastric adenocarcinoma) cell line. Materials and Methods: In this experimental study the AGS cell line was cultured in RPMI-1640, supplemented with penicillin/streptomycin (100 U/mL and 100 mg/mL, respectively) and 10% fetal bovine serum, at 37°C in a humidified atmosphere of 5% CO2. In 60 - 70% cell confluence, the cells were treated with curcumin concentration (20, 40, 100) μL and incubated for 24, 48 and 72 hours. Finally, total RNA were extracted and cDNA were synthesized and the expression of mentioned genes was detected. The data were analyzed by excel software. Results: Expression rate of OCT4A, OCT4B, Nanog and Nucleostemin (GLN3) at concentrations less than 20 μg/mL were reduced but OCT4B1 expression showed increased by hours respectively. Conclusions: The results showed that curcumin inhibited cell division; also, this study could be the basis for more extensive studies on the anti-cancer effect of the combined plants.

Inductions of Caspase-, MAPK- and ROS-dependent Apoptosis and Chemotherapeutic Effects Caused by an Ethanol Extract of Scutellaria barbata D. Don in Human Gastric Adenocarcinom Cells

Objectives:The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line).Methods:The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated.Results:ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin.Conclusion:ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria- , caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids

BackgroundGastric carcinoids are slow growing neuroendocrine tumours arising from enterochromaffin-like (ECL) cells in the corpus of stomach. Although most of these tumours arise in the setting of gastric atrophy and...

Isoprenaline Induces Periostin Expression in Gastric Cancer.

PurposePeriostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression.Materials and MethodsNormal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting.ResultsPeriostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells.ConclusionThese findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells.

Induction of Apoptosis and Cell Cycle Arrest by Dorema Glabrum Root Extracts in a Gastric Adenocarcinoma (AGS) Cell Line

Objective:Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells.Materials and Methods:The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression.Results:Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of 6.4 µg/ml and 4.6 µg/ml, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased.Conclusion:Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

Sulfotanone, a new alkyl sulfonic acid derivative from Streptomyces sp. IFM 11694 with TRAIL resistance-overcoming activity.

One new alkyl sulfonic acid derivative, sulfotanone (1), and the known panosialin wA (2) were isolated from the methanolic extract of mycelium of Streptomyces sp. 11694. The structure of the new compound (1) was established by a combination of spectroscopic techniques, including HRESIMS, IR, 1D and 2D NMR measurements. Compound 1 (40 µM) in combination with TRAIL showed synergistic activity in sensitizing TRAIL-resistance in human gastric adenocarcinoma cell lines.

Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression.

Background/AimsAstaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines.MethodsThe human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed.ResultsThe viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27kip-1 increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner.ConclusionsAstaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1.

Novel cytotoxic isobenzofuran derivatives from Streptomyces sp. IFM 11490

Three new isobenzofuran derivatives, named elmonin (1), elmenols A (2) and B (3), have been isolated from the ethyl acetate extract of the Streptomyces sp. IFM 11490. The structures of compounds 1–3 were established using extensive spectroscopic data analyses, including 1D and 2D NMR spectroscopy. The relative configuration of 2 was confirmed by single-crystal X-ray diffraction. Compounds 1 and 3 showed moderate cytotoxicity against the human gastric adenocarcinoma (AGS) cell line.

Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics

Background and ObjectivesIt can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. MethodsAll investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. ResultsUsing the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. ConclusionsWe showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.

국내산 및 수입산 참돔의 중금속 함량 및 항산화 활성과 세포독성 효과 비교

본 연구에서는 국내에서 주로 소비되는 국내산 및 수입산 참돔의 일반성분과 중금속 함량을 비교 분석하였고 생리활성을 비교하기 위하여 참돔을 용매의 극성에 따라 추출하여 항산화 및 세포독성 효과에 대해 연구하였다. 수입산과 비교했을 때 국내산 참돔은 높은 함량의 수분과 낮은 함량의 조지방, 조단백질 및 회분을 나타내었다. 국내산 및 수입산 참돔의 중금속 함량을 비교한 결과 원산지에 따른 유의적 차이를 보였으며 국내산 참돔의 수은 함량은 0.08 mg/kg으로 수입산 참돔보다 높은 함량을 나타내었으나 납의 경우 원산지에 따른 유의적 차이는 보이지 않았다. 국내산 및 수입산 참돔의 A+M 및 MeOH 추출물을 인체 섬유육종세포(HT-1080)에 처리하였을 때, 세포 내 활성산소종 생성 저해효과를 살펴 본 실험 결과, 국내산 및 수입산 참돔 추출물들에 의한 활성산소종 생성 억제효과를 비교해 보면 수입산 참돔 추출물에 의한 저해효과가 높았으며 두 추출물들 중 MeOH 추출물에 의한 저해효과가 높았음을 알 수 있었다. 인체 암세포들(AGS 및 HT-29)들에 대한 세포독성 활성 결과에서 AGS 암세포의 경우 국내산 참돔 A+M 및 MeOH 추출물들에 의한 세포독성 효과가 수입산 참돔A+M 추출물들보다 높았다. HT-29 암세포에 대해서는 국내산 참돔A+M 추출물에 의한 세포독성 효과가 수입산 참돔 A+M 추출물에 의한 것보다 높았고 MeOH 추출물에 의한 세포독성 효과는 유사했다. 따라서 본 연구 결과를 기초자료로 하여 향후 참돔의 다양한 생리활성 규명이 필요하다고 사료된다. This study compared the heavy metal contents and the effects of extracts from domestic and imported red sea bream on the antioxidant activity and cytotoxicity of human cancer cell lines. The antioxidant activity was measured using the fluorescently sensitive dye, 2&#x2019;-7&#x2019; dichlorofluorescein-diacetate (DCFH-DA), and antiproliferative activity against AGS human gastric adenocarcinoma and HT-29 human colon cancer cell lines, which was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Domestic red sea bream had a higher mercury content when compared to imported red sea bream, but there was no significant difference in the lead content. Treatments with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from domestic and imported red sea bream dose-dependently decreased the H₂O₂ induced ROS production, compared to the control. The cell viability showed that treatments with the A+M and MeOH extracts had cytotoxicity in the growth of AGS and HT-29 cancer cells. In the case of AGS, the extracts from the domestic red sea bream were higher in inhibiting cancer cell growth, compared to imported red sea bream. Our results demonstrate that the heavy metal contents of domestic and imported red sea bream were below the limit of the Food Code of Korea. The results of the biological activities indicate that the antioxidant activity of extracts from imported red sea bream was more effective, while the extracts from the domestic red sea bream were stronger in cytotoxic activity.

Coiled coil rich proteins (Ccrp) influence molecular pathogenicity of Helicobacter pylori.

Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen.

New Bioactive Chromanes from Litchi chinensis

Seven new δ-tocotrienols, designated litchtocotrienols A-G (1-7), together with one glorious macrocyclic analogue, macrolitchtocotrienol A (8), and one new meroditerpene chromane, cyclolitchtocotrienol A (9), were isolated from the leaves of Litchi chinensis. Their structures were mainly determined by extensive spectroscopic analysis, and their biological activities were evaluated by cytotoxicity against human gastric adenocarcinoma cell lines (AGS, ATCC CRL-1739) and hepatoma carcinoma cell line (HepG2 2.2.1.5). The structure-activity relationship of the isolated compounds was also discussed.

Transcriptome analysis reveals in vitro cultured Withania somnifera leaf and root tissues as a promising source for targeted withanolide biosynthesis.

BackgroundThe production of metabolites via in vitro culture is promoted by the availability of fully defined metabolic pathways. Withanolides, the major bioactive phytochemicals of Withania somnifera, have been well studied for their pharmacological activities. However, only a few attempts have been made to identify key candidate genes involved in withanolide biosynthesis. Understanding the steps involved in withanolide biosynthesis is essential for metabolic engineering of this plant to increase withanolide production.ResultsTranscriptome sequencing was performed on in vitro adventitious root and leaf tissues using the Illumina platform. We obtained a total of 177,156 assembled transcripts with an average unigene length of 1,033 bp. About 13% of the transcripts were unique to in vitro adventitious roots but no unique transcripts were observed in in vitro-grown leaves. A putative withanolide biosynthetic pathway was deduced by mapping the assembled transcripts to the KEGG database, and the expression of candidate withanolide biosynthesis genes -were validated by qRT PCR. The accumulation pattern of withaferin A and withanolide A varied according to the type of tissue and the culture period. Further, we demonstrated that in vitro leaf extracts exhibit anticancer activity against human gastric adenocarcinoma cell lines at sub G1 phase.ConclusionsWe report here a validated large-scale transcriptome data set and the potential biological activity of in vitro cultures of W. somnifera. This study provides important information to enhance tissue-specific expression and accumulation of secondary metabolites, paving the way for industrialization of in vitro cultures of W. somnifera.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1214-0) contains supplementary material, which is available to authorized users.

The Effects of Avocado Fruit Methanolic Extract on Human Gastric Adenocarcinoma Cell Line in Comparison with Peripheral Blood Mononuclear Cells

The Effects of Avocado Fruit Methanolic Extract on Human Gastric Adenocarcinoma Cell Line in Comparison with Peripheral Blood Mononuclear Cells Gastric cancer is the second leading cause of cancerrelated deaths in worldwide. Adenocarcinomas comprise the majority of stomach cancers that are usually diagnosed in the late stage with low survival rate and have prompted considerable interest in neo adjuvant therapies to improve longevity. It has been reported that neoplasias in the gastrointestinal system are mostly due to change in dietary habits. The therapeutic effect of herbal materials in suppression of cancer cell proliferation was shown. In this study, we evaluated the efficiency of methanolic extract of avocado fruit on the inhibition of growth of gastric adenocarcinoma cell line, in comparison with normal cells.

The photodynamic effect of far-red range phthalocyanines (AlPc and Pc green) supported by electropermeabilization in human gastric adenocarcinoma cells of sensitive and resistant type

IntroductionElectroporation (EP) is commonly applied for effective drug transport thorough cell membranes based on the application of electromagnetic field. When applied with cytostatics, it is called electrochemotherapy (ECT) – a quite new method of cancer treatment. A high-voltage pulse causes the formation of temporary pores in the cell membrane which create an additional way for the intracellular drug transport. In the current work, EP was effectively merged with the already known photodynamic therapy (PDT) to selective photosensitizers’ delivery to diseased tissue. The application of electroporation can reduce the dose of applied drug. Research objectiveThe aim of research was to evaluate the effectiveness of photodynamic reaction using two near infrared cyanines (AlPc and Pc green) combined with electroporation in two human gastric adenocarcinoma cell lines. Materials and methodsTwo human cell lines – EPG85-257P (parental) and EPG85-257RDB (resistant to daunorubicin) – of gastric cancer were used. The effect of two photosensitizers (aluminum 1,8,15,22-tetrakis(-phenylthio)-29H,31H-phthalocyanine chloride and Phthalocyanine green) was investigated. The efficiency of EP parameters was assessed by propidium iodide uptake. The viability assay was applied to analyse EP, PDT and EP-PDT effect. Cyanine localization was determined by confocal microscopy. Immunocytochemical evaluation of manganese superoxide dismutase and glutathione S-transferase-pi was determined after applied therapies. ResultsPDT in combination with EP affected the viability of EPG85-257P and EPG85-257RDB cells negatively while both cyanine were used. The most evident changes were observed in the following concentrations: 15, 10 and 5μM. The optimal field strength for enhanced EP-PDT was 800 and 1200V/cm. AlPc distributed selectively in the lysosomes of parental cell line. ConclusionsPDT, enhanced by EP, caused decreased viability when compared to the application of PDT alone. Both phthalocyanines found to be more effective after electroporation. Due to the low concentration of light-sensitive compounds and safety of electroporation itself, a treatment plan can be an alternative therapeutic modality against gastric adenocarcinomas.

Probing the origins of anticancer activity of chrysin derivatives

Chrysin is a derivative of flavonoid, a natural product commonly found in plants. It has been shown to afford a wide variety of pharmacological activities particularly anticancer properties. In this study, 21 chrysin derivatives with anticancer activities against human gastric adenocarcinoma (SGC-7901) and human colorectal adenocarcinoma (HT-29) cell lines were employed for quantitative structure–activity relationship (QSAR) investigation. Molecular structures were geometrically optimized at the B3LYP/6-311++g(d,p) level and their quantum chemical and molecular properties were obtained from Gaussian 09 and Dragon softwares, respectively. Significant descriptors for modeling the anticancer activities of SGC-7901 (i.e., SIC2, Mor11e, P2p, HTp, and R5e+) and HT-29 (i.e., L/Bw, BIC2, and Mor19p) cell lines were deduced from stepwise multiple linear regression (MLR) method. QSAR models were constructed using MLR and their predictivities were verified via internal (i.e., leave one-out cross-validation; LOO-CV) and external sets. The predictive performance was evaluated from their squared correlation coefficients (R2 and Q2) and root mean square error (RMSE). Results indicated good correlation between experimental and predicted anticancer activities as deduced from statistical parameters of internal and external sets as follows: RTr2 = 0.8778, RMSETr = 0.0854, QCV2 = 0.7315, RMSECV = 0.1375, QExt2 = 0.7324, and RMSEExt = 0.1168 for QSAR models of SGC-7901 while RTr2 = 0.8201, RMSETr = 0.1293, QCV2 = 0.6829, RMSECV = 0.1735, QExt2 = 0.8486, and RMSEExt = 0.1179 for QSAR models of HT-29. Furthermore, the obtained QSAR models provided pertinent insights on the structure–activity relationship of investigated compounds where molecular properties such as shape, electronegativities and polarizabilities were crucial for anticancer activity. The knowledge gained from the constructed QSAR models could serve as guidelines for the rational design of novel chrysin derivatives with potent anticancer activity.