Effect of ADM on Proliferation and Apoptosis of Human Gastric Cancer Cell SGC-7901

2012 ◽  
Vol 535-537 ◽  
pp. 2434-2437
Author(s):  
Shu Li Shao ◽  
Wei Wei Chen ◽  
Wei Wei Zhang ◽  
Wei Zhao ◽  
Feng Ying Li
Keyword(s):  
Flow Cytometry ◽  
Human Gastric Cancer ◽  
Agarose Gel ◽  
Dna Ladder ◽  
Cell Cycles ◽  
Proliferation And Apoptosis ◽  
Ic50 Values ◽  
Cellular Apoptosis ◽  
Blue Stain ◽  
Morphologic Changes

To observe the effect of ADM on cells apoptosis of SGC-7901 cells. The SGC-7901 cells were treated by ADM. And the inhibitory ratio of cells was measured by trypan blue stain assay, the IC50 value was calculated. Cells apoptosis were detected by DNA agarose gel electrophoresis.The cell cycles were analyzed by flow cytometry system after treatment with ADM. Morphologic changes were observed using phase-contrast microscopy . The SGC-7901 cells proliferation were remarkably inhibited by ADM. The IC50 values were 5.7 μg / mL. The typical DNA ladder on agarose gel electrophoresis for analysis of cellular apoptosis were significantly appeared. ADM could restrain the SGC-7901 cells proliferation, and to cause the morphologic changes of apoptosis. Apoptosis peaks appeared with flow cytometry analysis.

Design, Synthesis and Biological Evaluation: 5-amino-1H-pyrazole-1- carbonyl derivatives as FGFR Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1330-1341
Author(s):  
Yan Zhang ◽  
Niefang Yu
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Gastric Cancer ◽  
Design Synthesis ◽  
Carbonyl Derivatives ◽  
Ic50 Values ◽  
Inhibitory Activities

Background: Fibroblast growth factors (FGFs) and their high affinity receptors (FGFRs) play a major role in cell proliferation, differentiation, migration, and apoptosis. Aberrant FGFR signaling pathway might accelerate development in a broad panel of malignant solid tumors. However, the full application of most existing small molecule FGFR inhibitors has become a challenge due to the potential target mutation. Hence, it has attracted a great deal of attention from both academic and industrial fields for hunting for novel FGFR inhibitors with potent inhibitory activities and high selectivity. Objective: Novel 5-amino-1H-pyrazole-1-carbonyl derivatives were designed, synthesized, and evaluated as FGFR inhibitors. Methods: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives were established by a condensation of the suitable formyl acetonitrile derivatives with either hydrazine or hydrazide derivatives in the presence of anhydrous ethanol or toluene. The inhibitory activities of the target compounds were screened against the FGFRs and two representative cancer cell lines. Tests were carried out to observe the inhibition of 8e against FGFR phosphorylation and downstream signal phosphorylation in human gastric cancer cell lines (SNU-16). The molecular docking of all the compounds were performed using Molecular Operating Environment in order to evaluate their binding abilities with the corresponding protein kinase. Results: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives have been designed and synthesized, screened for their inhibitory activities against FGFRs and cancer cell lines. Most of the target compounds showed moderate to good anti-proliferate activities against the tested enzymes and cell lines. The most promising compounds 8e suppressed FGFR1-3 with IC50 values of 56.4, 35.2, 95.5 nM, and potently inhibited the SNU-16 and MCF-7 cancer cells with IC50 values of 0.71 1.26 μM, respectively. And 8e inhibited the growth of cancer cells containing FGFR activated by multiple mechanisms. In addition, the binding interactions were quite similar in the molecular models between generated compounds and Debio-1347 with the FGFR1. Conclusion: According to the experimental findings, 5-amino-1H-pyrazole-1-carbonyl might serve as a promising template of an FGFR inhibitor.

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

2021 ◽  
Vol 21 ◽  
Author(s):  
Nishtha Shalmali ◽  
Sandhya Bawa ◽  
Md Rahmat Ali ◽  
Sourav Kalra ◽  
Raj Kumar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Active Sites ◽  
Colorectal Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Adenocarcinoma Cells ◽  
Ic50 Values

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 µM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 µM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 µM and 106.91 µM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

Growth Inhibition of Nasopharyngeal Carcinoma Cells Mediated by p53 Gene-Containing Nanolipid Composites

2020 ◽  
Vol 20 (10) ◽  
pp. 6026-6032
Author(s):  
Yongshan Cheng ◽  
Shanying Wu ◽  
Xinting Tie ◽  
Xiaodong Huang ◽  
Lihua Cui
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Nasopharyngeal Carcinoma ◽  
Growth Inhibition ◽  
Transfection Efficiency ◽  
P53 Gene ◽  
Theoretical Support ◽  
Novel Drugs ◽  
Cellular Apoptosis

To study the growth inhibition and cell cycle changes in nasopharyngeal carcinoma (CNE1) cells after transfection with p53 gene. A mixture of nano-liposomes and plasmid containing p53 was used for transfecting CNE1 cells. Cellular apoptosis was examined after transfection using the CCK-8 reagent method with flow cytometry. The results showed that a ratio of nanoliposome/p-ORF-GFP of 3.5:1 showed the highest transfection efficiency in CNE1 cells. The cells transfected with a mixture of composites in this proportion showed significant apoptosis of up to 50–70%. In addition, we observed that cell cycle changes-measured using flow cytometry-as well as cellular apoptosis were accelerated after administration of composites. The CCK-8 kit was used to determine the viability of nano-liposome-encapsulated p53 transfected cells. In vitro experiments showed that the combination significantly inhibited the growth of CNE1 cells with an inhibition rate of approximately 63.8%. Therefore, the nanocomposites have a significant effect on inhibiting the growth of CNE1 cells. Through the investigation of apoptosis and cell cycle changes in CNE1 cells we found that the nanoliposome-encapsulated p53 gene can inhibit growth in these cells, and might therefore serve as a novel treatment strategy for adjuvant treatment of nasopharyngeal carcinoma and ca also reduce incompatibility issues with radiotherapy and chemotherapy. This method can also provide technical and theoretical support for the development of novel drugs.

scholarly journals Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yi Shi ◽  
Xiaofei Mo ◽  
Simei Hong ◽  
Tianbao Li ◽  
Baozhen Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Resistant Cell ◽  
Therapeutic Drug ◽  
Specific Gene ◽  
Sorafenib Treatment ◽  
Proliferation And Apoptosis

Sorafenib is the first FDA-approved therapeutic drug for molecular target medication on advanced-stage hepatocellular carcinoma. It is reported that sorafenib could improve the survival of progression-free patients for 4 to 6 months; however, most of the patients developed drug resistance. Thus, it is critical to reveal the biological mechanisms behind sorafenib resistance. In this study, a sorafenib-resistant model was developed by exposing HepG2 cells to sorafenib with gradient increasing concentration, and the resistance-related genes were screened by microarray. Real-time qPCR was used to validate selected gene expression of the resistance model, and lentivirus vector-mediated RNA interference was applied for specific gene knockdown. In addition, high-throughput High Celigo Select (HCS) and flow cytometry were used to measure the effect on cellular proliferation and apoptosis. As a result, our study established a sorafenib-resistant model with IC50 of 9.988 μM. The Affymetrix expression profile of the sorafenib-resistant model showed 35 resistant-related genes, and 91.4% of the resistant genes showed upregulation in HepG2 resistance cells. In addition, 20 genes were knocked down to measure cell proliferation, and MAP4K3 with high proliferation inhibiting phenotype was chosen for further study. Meanwhile, the HCS results revealed that shMAP4K3 transfection could downregulate resistant cell proliferation, and the flow cytometry results showed that cell apoptosis was significantly increased in the MAP4K3 knockdown group. In summary, MAP4K3 is a novel molecular marker for improving the drug sensitivity of sorafenib treatment in hepatocellular carcinoma.

scholarly journals Chemical Constituents of Stems and Leaves of Tagetespatula L. and Its Fingerprint

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3911 ◽  
Author(s):  
Yu-Meng Wang ◽  
Xiao-Ku Ran ◽  
Muhammad Riaz ◽  
Miao Yu ◽  
Qian Cai ◽  
...  
Keyword(s):  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Chemical Constituents ◽  
Human Gastric Cancer ◽  
Chemical Structures ◽  
Yellow Color ◽  
Ic50 Values ◽  
Gastric Cancer Cell Lines ◽  
Stems And Leaves

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3–16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

scholarly journals ΔNp63α mediates proliferation and apoptosis in human gastric cancer cells by the regulation of GATA-6

Neoplasma ◽  
2012 ◽  
Vol 59 (04) ◽  
pp. 416-423 ◽  
Author(s):  
H. WANG ◽  
Z. LIU ◽  
J. LI ◽  
X. ZHAO ◽  
Z. WANG ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Proliferation And Apoptosis

scholarly journals Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol

2002 ◽  
Vol 9 (1-2) ◽  
pp. 33-43 ◽  
Author(s):  
Gordana Bogdanović ◽  
Vesna Kojić ◽  
Tatjana Srdić ◽  
Dimitar Jakimov ◽  
Miloš I. Djuran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Recovery Period ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
Mcf7 Cells ◽  
Cisplatin Analogues ◽  
Ic50 Values ◽  
G2m Phase ◽  
Induced Apoptosis

The platinum (II)complexes, cis-[PtCl2(CH3SCH2CH2SCH3)] (Pt1), cis-[PtCl2(dmso)2] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl2(NH3)2] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis.MCF7 cells were found to be sensitive to both Pt1 and Pt2 complexe These cisplatin analogues influenced the cell growth more effectively as compared to cisplatin. Cytotoxic effect was concentration and time-dependent. Profound growth inhibitory effect was observed for Pt1 complex, across all its concentrations at all recovery periods. A plateau effect was achieved three days after treatment at Pt1 concentrations ≤ 1 μM. Pt2, however, decreased MCF7 cells survival only for the first 24 h ranging between 50-55%. Pt2 cytotoxicity sharply decreased thereafter, approaching 2 h - treatment cytotoxicity level. The median IC50 values for Pt1 and Pt2 were similar (0.337 and 0.3051 μM, respectively) but only for the first 24 h. The IC50 values for Pt1 strongly depend on the recovery period. On simultaneos exposure of cells to taxol and platinum(II) complexes no consistent effect was found. The Cls for combinations of taxol with Pt1 or Pt2 revealed cytotoxic effects that were in most Cases synergistic (Pt1) or less than addtiive (Pt2). Flow cytometry analysis has shown that each platinum(II) complex induced apoptosis in MCF7 cells. The level of apoptosis correlated with cytotoxicity level for the range concentrations. Both cisplatin analogues, at IC50 concentrations, increased the number of MCF7 cells in G0G1 phase of cell cycle. Pt2-treated cells remained arrested in G0G1 phase up to 72 h after treatment. Combination of Pt2 and taxol caused further arrest of cells in G0G1 phase (24 h) in parallel with strong decrement of G2M phase cells.

scholarly journals The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

2018 ◽  
Vol 47 (3) ◽  
pp. 981-993 ◽  
Author(s):  
Yu Chen ◽  
Tongtong Wang ◽  
Jing Du ◽  
Yanchun Li ◽  
Xin Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Proliferation And Apoptosis ◽  
And Migration

Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML.

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