scholarly journals Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4187
Author(s):  
Chun Han ◽  
Kemin Shen ◽  
Shijun Wang ◽  
Zhijun Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Dependent Manner ◽  
Binding Modes ◽  
A431 Cells ◽  
Docking Analysis ◽  
Antiproliferative Effects ◽  
Substituted Benzamides ◽  
G2 Phase ◽  
Induced Apoptosis ◽  
Dose Dependent

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

scholarly journals Biofabricated Fatty Acids-Capped Silver Nanoparticles as Potential Antibacterial, Antifungal, Antibiofilm and Anticancer Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 139
Author(s):  
Mohammad Azam Ansari ◽  
Sarah Mousa Maadi Asiri ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Ahmad Almatroudi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Silver Nanoparticles ◽  
Anticancer Agents ◽  
Sem Analysis ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Anticancer Efficacy ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Dose Dependent

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.

scholarly journals Nonylphenol Induces Apoptosis through ROS/JNK Signaling in a Spermatogonia Cell Line

2020 ◽  
Vol 22 (1) ◽  
pp. 307
Author(s):  
Hyun-Jung Park ◽  
Ran Lee ◽  
Hyunjin Yoo ◽  
Kwonho Hong ◽  
Hyuk Song
Keyword(s):  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Ros Generation ◽  
Dependent Manner ◽  
Jnk Signaling ◽  
Apoptosis Markers ◽  
Testicular Size ◽  
Spermatogonia Cell ◽  
Induced Apoptosis ◽  
Dose Dependent

Nonylphenol (NP) is an endocrine-disruptor chemical that negatively affects reproductive health. Testes exposure to NP results in testicular structure disruption and a reduction in testicular size and testosterone levels. However, the effects of NP on spermatogonia in testes have not been fully elucidated. In this study, the molecular mechanisms of NP in GC-1 spermatogonia (spg) cells were investigated. We found that cell viability significantly decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to NP. Furthermore, the expression levels of the pro-apoptotic proteins increased, whereas anti-apoptosis markers decreased in NP-exposed GC-1 spg cells. We also found that NP increased reactive oxygen species (ROS) generation, suggesting that ROS-induced activation of the MAPK signaling pathway is the molecular mechanism of NP-induced apoptosis in GC-1 spg cells. Thus, NP could induce c-Jun phosphorylation; dose-dependent expression of JNK, MKK4, p53, and p38; and the subsequent inhibition of ERK1/2 and MEK1/2 phosphorylation. The genes involved in apoptosis and JNK signaling were also upregulated in GC-1 spg cells treated with NP compared to those in the controls. Our findings suggest that NP induces apoptosis through ROS/JNK signaling in GC-1 spg cells.

Dexamethasone-Induced Apoptosis of Human Monocytes Exposed to Immune Complexes. Intervention of CD95-and Xiap-Dependent Pathways

2005 ◽  
Vol 18 (3) ◽  
pp. 403-415 ◽  
Author(s):  
L. Ottonello ◽  
M. Bertolotto ◽  
F. Montecucco ◽  
P. Dapino ◽  
F. Dallegri
Keyword(s):  
Immune Complex ◽  
Immune Complexes ◽  
Therapeutic Option ◽  
Mek Inhibitor ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Inflammatory Reactions ◽  
Activated Monocytes ◽  
Induced Apoptosis ◽  
Dose Dependent

Monocytes and macrophages play a key role in the initiation and persistence of inflammatory reactions. The possibility to interfere with the survival of these cells, once recruited and activated at sites of inflammation, is an attractive therapeutic option. Although resting monocytes are susceptible to pharmacologically induced apoptosis, no data are available about the possibility to modulate the survival of activated monocytes. The present work was planned to investigate if dexamethasone is able to promote apoptosis of human monocytes activated by immune complexes. When monocytes were cultured with immune complexes, a dose-dependent inhibition of apoptosis was observed. Dexamethasone stimulated apoptosis of resting and activated monocytes in a dose-dependent manner. Both the immune complex inhibitory activity and dexamethasone stimulatory properties depend on NF-kB/XIAP and Ras/MEK/ERK/CD95 pathways. In fact, the exposure of monocytes to immune complexes increased NF-kB activation and XIAP expression, which in turn were inhibited by dexamethasone. On the other hand, immune complex-stimulated monocytes displayed a reduced expression of CD95, which is prevented by dexamethasone, as well as by MEK inhibitor U0126. Furthermore, anti-CD95 ZB4 mAb prevented dexamethasone-induced apoptosis in immune complex-stimulated monocytes. Similarly, ZB4 inhibited dexamethasone-mediated augmentation of caspase 3 activity. The present findings suggest that Fc triggering by insoluble immune complexes result in the activation of two intracellular pathways crucial for the survival of monocytes: 1. Ras/MEK/ERK pathway responsible for the down-regulation of CD95 expression; 2. NF-kB pathway governing the expression of XIAP. Both the pathways are susceptible to inhibition by monocyte treatment with pharmacologic concentrations of dexamethasone.

scholarly journals Emodin promotes apoptosis of human endometrial cancer through regulating the MAPK and PI3K/ AKT pathways

2019 ◽  
Vol 13 (1) ◽  
pp. 489-496 ◽  
Author(s):  
Jun Jiang ◽  
Nanyang Zhou ◽  
Pian Ying ◽  
Ting Zhang ◽  
Ruojia Liang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathways ◽  
Tumor Development ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Western Blot Assay ◽  
Anti Oxidant ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Dose Dependent

AbstractEmodin, a major component of rhubarb, has anti-tumor effects in a variety of cancers, influencing multiple steps of tumor development through modulating several signaling pathways. The aim of this study is to examine the effect of emodin on cell apoptosis and explore the underlying mechanisms in human endometrial cancer cells. Here we report that emodin can inhibit KLE cell proliferation and induce apoptosis in a time- and dose-dependent manner. Western blot assay found that emodin was involved in MAPK and PI3K/Akt signaling pathways. Specifically, emodin significantly suppressed the phosphorylation of AKT, and enhanced the phosphorylation of MAPK pathways. Furthermore, the generation of reactive oxygen species (ROS) was up-regulated in KLE cells upon treatment with emodin, while the anti-oxidant agent N-acetyl cysteine (NAC) can inhibit emodin-induced apoptosis and promote the activation of AKT and Bcl-2. Taken together, we revealed that emodin may induce apoptosis in KLE cells through regulating the PI3K/AKT and MAPK signaling pathways, indicating the importance of emodin as an anti-tumor agent.

Effect of Hydroxyapatite Nanoparticles of Different Concentrations on Rat Osteoblast

2009 ◽  
Vol 610-613 ◽  
pp. 1364-1369 ◽  
Author(s):  
Zheng Li Xu ◽  
Jiao Sun ◽  
Chang Sheng Liu ◽  
Jie Wei
Keyword(s):  
Specific Surface ◽  
Surface Area ◽  
Specific Surface Area ◽  
Control Group ◽  
Dependent Manner ◽  
Hydroxyapatite Nanoparticles ◽  
Inhibition Ratio ◽  
Rat Osteoblast ◽  
Induced Apoptosis ◽  
Dose Dependent

Nano-HAP (10-20nm) were obtained from East China University of Science and Technology. The osteoblasts were primary cultured from rat calvaria and then treated with five different concentrations(20，40，60，80，100µg/ml) of nano-HAP, the osteoblasts without nano-HAP was used as control group. Inhibition ratio, apoptotic rate were evaluated by MTT assay and flow cytometry (FCM), respectively. The specific surface area of nano-HAP was detected by BET. All date were expressed as mean ± standard deviation.Statistical analysis was performed by t test using software SPSS11.0 for Windows. The results indicated that the nano-HAP could inhibit the growth of osteoblasts in a dose-dependent manner. When the concentrations of nano-HAP were 20, 40, 60, 80, 100µg/ml, the inhibition ratio were 2.8%, 22.2%, 26.9%, 38% and 47.7%, and the apoptotic rate were 4.63%, 6.75%, 9.47%, 11.49%, 17.22%, respectively, which were obviously higher than that of control group. The nano-HAP significantly induced apoptosis in osteoblasts. There were the same tendency that the apoptotic and inhibition ratio of osteoblasts were rising with the increasing of the concentration of the nano-HAP. The specific surface area of nano-HAP was 148.140m2/g.

scholarly journals Neural stem cell conditioned medium alleviates Aβ25-35 damage to SH-SY5Y cells through the PCMT1/MST1 pathway

2020 ◽  
Author(s):  
Guoyong Jia ◽  
Hongna Yang ◽  
Zengyan Diao ◽  
Ying Liu ◽  
Congcong Sun
Keyword(s):  
Stem Cell ◽  
Cell Viability ◽  
Conditioned Medium ◽  
Neural Stem Cell ◽  
Inhibitory Effect ◽  
Complete Medium ◽  
Dependent Manner ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Cell Conditioned Medium

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that protein isoaspartate methyltransferase 1 (PCMT1) is highly expressed in brain tissue (substantia nigra, blue plaque, paraventricular nucleus). In this study, we investigated the effect of neural stem cell conditioned medium alleviates Aβ25-35 damage to SH-SY5Y cells by PCMT1/MST1 pathway. Results demonstrated that Aβ25-35 significantly decreased the cell viability in time and dose dependent manner. However, Neural stem cell-complete medium (NSC-CPM) or NSC-CDM had inhibitory effect on toxicity when fibrillation of Aβ25-35 occurred in their presence and NSC-CDM had a better inhibitor result. An increase of the PCMT1 expression levels was found in Aβ25-35 + NSC-CDM group. sh-PCMT1 significantly reduced the PCMT1, the cell viability and inhibited the protective effect; induced apoptosis and increased the expression of p-MST1. Overexpression of PCMT1 group reversed the effect of Aβ25-35 inhibited the cell viability and Aβ25-35 induced the apoptosis. In conclusion, NSC-CDM corrects the damage of Aβ25-35 to cells by increasing PCMT1, reducing MST phosphorylation.

SMBA1, a Bax Activator, Induces Cell Cycle Arrest and Apoptosis in Malignant Glioma Cells

Pharmacology ◽  
2019 ◽  
Vol 105 (3-4) ◽  
pp. 164-172
Author(s):  
Shuangbo Fan ◽  
Qian Xu ◽  
Liang Wang ◽  
Yulin Wan ◽  
Sheng Qiu
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Biological Effects ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
Cycle Arrest ◽  
Intrinsic Apoptosis Pathway ◽  
Induced Apoptosis ◽  
Dose Dependent

SMBA1 (small-molecule Bax agonists 1), a small molecular activator of Bax, is a potential anti-tumour agent. In the present study, we investigated the biological effects of SMBA1 on glioblastoma (GBM) cells. SMBA1 reduced the viabilities of U87MG, U251 and T98G cells in a time- and dose-dependent manner. Moreover, treatment with SMBA1 induced cell cycle arrest at the G2/M phase transition, accompanied by the downregulation of Cdc25c and cyclin B1 and the upregulation of p21. SMBA1 also induced apoptosis of GBM cells in a dose-dependent manner. Mechanistically, SMBA1 induced apoptosis via the intrinsic pathway. Silencing of Bax or ectopic expression of Bcl-2 significantly inhibited SMBA1-induced apoptosis. Moreover, SMBA1 inhibited the growth of U87MG xenograft tumours in vivo. Overall, SMBA1 shows anti-proliferative effects against GBM cells through activation of the intrinsic apoptosis pathway.

Effects of Stearic Acid on Proliferation, Differentiation, Apoptosis, and Autophagy in Porcine Intestinal Epithelial Cells

2020 ◽  
Vol 20 (2) ◽  
pp. 157-166
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Stearic Acid ◽  
Er Stress ◽  
Intestinal Epithelial Cells ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent

Background: Stearic acid (SA), a saturated long-chain fatty acid consisting of 18 carbon atoms, is widely found in feed ingredients, such as corn, soybeans, and wheat. However, the roles of SA in the renewal of intestinal epithelial cells remain unclear. Methods and Results: In the present study, we found that 0.01-0.1 mM SA promoted IPEC-J2 cell differentiation and did not affect IPEC-J2 cell viability. In addition, the results showed that the viability of IPEC-J2 cells was inhibited by SA in a time- and dose-dependent manner at high concentrations. Flow cytometry and western blot analysis suggested that SA induced apoptosis, autophagy and ER stress in cells. In addition, the amounts of triglyceride were significantly increased upon challenge with SA. Moreover, the decrease in the viability of cells induced by SA could be attenuated by 4-PBA, an inhibitor of ER stress. Conclusion: In summary, SA accelerated IPEC-J2 cell differentiation at 0.01-0.1 mM. Furthermore, SA induced IPEC-J2 cell apoptosis and autophagy by causing ER stress.

scholarly journals Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 964 ◽  
Author(s):  
Darja Koutova ◽  
Monika Kulhava ◽  
Radim Havelek ◽  
Martina Majorosova ◽  
Karel Královec ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Dependent Manner ◽  
Carcinoma Cell Lines ◽  
Ic50 Values ◽  
Bisbenzylisoquinoline Alkaloid ◽  
Human Leukemic Cells ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Increased Activity ◽  
Mcf 7

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.

scholarly journals Autophagy Inhibition Enhances Apoptosis Induced by Dioscin in Huh7 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ming-Ju Hsieh ◽  
Shun-Fa Yang ◽  
Yih-Shou Hsieh ◽  
Tzy-Yen Chen ◽  
Hui-Ling Chiou
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Natural Food ◽  
Dependent Manner ◽  
Caspase Activation ◽  
Huh7 Cells ◽  
Dependent Cell ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Autophagy Inhibition

Extensive research results support the application of herbal medicine or natural food as an augment during therapy for various cancers. However, the effect of dioscin on tumor cells autophagy has not been clearly clarified. In this study, the unique effects of dioscin on autophagy of hepatoma cells were investigated. Results found that dioscin induced caspase-3- and -9-dependent cell apoptosis in a dose-dependent manner. Moreover, inhibition of ERK1/2 phosphorylation significantly abolished the dioscin-induced apoptosis. In addition, dioscin triggered cell autophagy in early stages. With autophagy inhibitors to hinder the autophagy process, dioscin-induced cell apoptosis was significantly enhanced. An inhibition of caspase activation did not affect the dioscin-induced LC3-II protein expression. Based on the results, we believed that while apoptosis was blocked, dioscin-induced autophagy process also diminished in Huh7 cells. In conclusion, this study indicates that dioscin causes autophagy in Huh7 cells and suggests that dioscin has a cytoprotective effect.

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