scholarly journals Identification of Compound CB-2 as a Novel Late-Stage Autophagy Inhibitor Exhibits Inhibitory Potency against A549 Cells

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 865
Author(s):  
Zhihui Liu ◽  
Lu Zhang ◽  
Yachao Liu ◽  
Hanxiao Zhang ◽  
Jingxuan Chen ◽  
...  
Keyword(s):  
Late Stage ◽  
A549 Cells ◽  
Treatment Resistance ◽  
Inhibitory Effect ◽  
High Dose ◽  
Inhibitory Potency ◽  
Curcumin Derivatives ◽  
Autophagy Inhibitor ◽  
Autophagy Induction ◽  
Apoptosis And Necrosis

Autophagy has been recognized as a stress tolerance mechanism that maintains cell viability, which contributes to tumor progression, dormancy, and treatment resistance. The inhibition of autophagy in cancer has the potential to improve the therapeutic efficacy. It is therefore of great significance to search for new autophagy inhibitors. In the present study, after screening a series of curcumin derivatives synthesized in our laboratory, (E)-3-((E)-4-chlorobenzylidene)-5-((5-methoxy-1H-indol-3-yl)methylene)-1-methylpiperidin-4-one (CB-2) was selected as a candidate for further study. We found that CB-2 increased the LC3B-II and SQSTM1 levels associated with the accumulation of autophagosomes in non-small cell lung cancer (NSCLC) A549 cells. The increased level of LC3B-II induced by CB-2 was neither eliminated when autophagy initiation was suppressed by wortmannin nor further increased when autophagosome degradation was inhibited by chloroquine (CQ). CB-2 enhanced the accumulation of LC3B-II under starvation conditions. Further studies revealed that CB-2 did not affect the levels of the key proteins involved in autophagy induction but significantly blocked the fusion of autophagosomes with lysosomes. High-dose CB-2 induced the apoptosis and necrosis of A549 cells, while a lower dose of CB-2 mainly impaired the migrative capacity of A549 cells, which only slightly induced cell apoptosis. CB-2 increased the levels of mitochondrial-derived reactive oxygen species (ROS) while decreasing the mitochondrial membrane potential (MMP). Scavenging ROS via N-acetylcysteine (NAC) reversed CB-2-induced autophagy inhibition and its inhibitory effect against A549 cells. In conclusion, CB-2 serves as a new late-stage autophagy inhibitor, which has a strong inhibitory potency against A549 cells.

Heparin Counteracts the Antiaggregating Effect of Prostacyclin by Potentiating Platelet Aggregation

1983 ◽  
Vol 49 (02) ◽  
pp. 081-083 ◽  
Author(s):  
Vittorio Bertelé ◽  
Maria Carla Roncaglioni ◽  
Maria Benedetta Donati ◽  
Giovanni de Gaetano
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Specific Interaction ◽  
Inhibitory Effect ◽  
Effective Inhibitor ◽  
Inhibitory Potency ◽  
Human Platelet Aggregation

SummaryIt has recently been reported that heparin neutralizes the inhibitory effect of prostacyclin (PGI2) on human platelet aggregation. The mechanism of this interaction has not yet been unequivocally established. We present here evidence that heparin (Liquemin Roche) does not react directly with PGI2 but counteracts its inhibitory effect by potentiating platelet aggregation. In the absence of heparin, PGI2 was a less effective inhibitor of platelet aggregation induced by the combination of ADP and serotonin than by ADP alone. Moreover, the inhibitory effect of PGI2 was similarly reduced when increasing the concentrations of ADP (in the absence of heparin). The lack of a specific interaction between heparin and PGI2 is supported by the observation that, in the presence of heparin, other prostaglandins such as PGD2 and PGE1, and a non-prostanoid compound such as adenosine also appeared to lose their inhibitory potency. It is concluded that heparin opposes platelet aggregation inhibitory effect of PGI2 by enhancement of platelet aggregation.

Curcumin-based antioxidant and glycohydrolase inhibitor compounds: Synthesis and in vitro appraisal of the dual activity against diabetes

2020 ◽  
Vol 16 ◽  
Author(s):  
Sajjad Esmaeili ◽  
Nazanin Ghobadi ◽  
Donya Nazari ◽  
Alireza Pourhossein ◽  
Hassan Rasouli ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Enzyme Inhibitor ◽  
Radical Scavenging Activity ◽  
Curcuma Longa ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Inhibitory Effect ◽  
Curcumin Derivatives ◽  
Reducing Power Assay

Background: Curcumin, as the substantial constituent of the turmeric plant (Curcuma longa), plays a significant role in the prevention of various diseases, including diabetes. It possesses ideal structure features as enzyme inhibitor, including a flexible backbone, hydrophobic nature, and several available hydrogen bond (H-bond) donors and acceptors. Objective: The present study aimed at synthesizing several novel curcumin derivatives and further evaluation of these compounds for possible antioxidant and anti-diabetic properties along with inhibitory effect against two carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, as these enzymes are therapeutic targets for attenuation of postprandial hyperglycemia. Methods: Therefore, curcumin-based pyrido[2,3-d]pyrimidine derivatives were synthesized and identified using an instrumental technique like NMR spectroscopy and then screened for antioxidant and enzyme inhibitory potential. Total antioxidant activity, reducing power assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH• ) radical scavenging activity were done to appraisal the antioxidant potential of these compounds in vitro. Results: Compounds L6-L9 showed higher antioxidant activity while L4, L9, L12 and especially L8 exhibited the best selectivity index (lowest α-amylase/α-glucosidase inhibition ratio). Conclusion: These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index but also to limit the activity of the major reactive oxygen species (ROS) producing pathways.

Pseudo-Parkinson Disease Secondary to Ritonavir–Buspirone Interaction

2003 ◽  
Vol 37 (2) ◽  
pp. 202-205 ◽  
Author(s):  
Patrick G Clay ◽  
Molly M Adams
Keyword(s):  
Drug Interaction ◽  
Inhibitory Effect ◽  
Hiv Positive ◽  
High Dose ◽  
Resting Tremor ◽  
Case Summary ◽  
History Of ◽  
Drug Drug Interaction ◽  
To Receive

OBJECTIVE: To report a case of Parkinson-like symptoms appearing in a patient after introduction of ritonavir to buspirone therapy. CASE SUMMARY: A 54-year-old HIV-positive white man presented to the clinic with a 2-week history of ataxia, shuffling gait, cogwheel rigidity, resting tremor, and sad affect with masked features. This patient had been receiving high-dose buspirone (40 mg every morning and 30 mg every evening) for 2 years prior to the introduction of ritonavir/indinavir combination therapy (400 mg/400 mg twice daily) 6 weeks prior to initiation of the above symptoms. Buspirone was decreased to 15 mg 3 times daily, ritonavir/indinavir was discontinued, and amprenavir 1200 mg twice daily was added. The patient's symptoms began to subside after 1 week, with complete resolution after about 2 weeks. The patient continued to receive buspirone for an additional 12 months without recurrence of symptoms. DISCUSSION: This is the first reported interaction of buspirone and antiretrovirals. Buspirone, extensively metabolized by CYP3A4, was likely at supratherapeutic levels due to the inhibitory effect of ritonavir and, secondarily, indinavir. The Parkinson-like symptoms developed rapidly and severely, impacted this patient's quality of life, and necessitated significant clinic expenditures to identify this drug–drug interaction. CONCLUSIONS: This case demonstrates a severe drug–drug interaction between buspirone and ritonavir and further demonstrates the need for awareness of the metabolic profile for all agents an HIV-infected patient is receiving.

scholarly journals Inhibitory Effect of thePunica granatumFruit Extract on Angiotensin-II Type I Receptor and Thromboxane B2 in Endothelial Cells Induced by Plasma from Preeclamptic Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Widya Kusumawati ◽  
Kusnarman Keman ◽  
Setyawati Soeharto
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Vascular Endothelial Cells ◽  
Ethanolic Extract ◽  
Punica Granatum ◽  
Normal Pregnancy ◽  
Inhibitory Effect ◽  
Thromboxane B2 ◽  
High Dose ◽  
Type I

This study aims to evaluate whether thePunica granatumfruit extract modulates the Angiotensin-II Type I receptor (AT1-R) and thromboxane B2 level in endothelial cells induced by plasma from preeclamptic patients. Endothelial cells were obtained from human umbilical vascular endothelial cells. At confluence, endothelial cells were divided into five groups, which included endothelial cells exposed to 2% plasma from normal pregnancy (NP), endothelial cells exposed to 2% plasma from preeclamptic patients (PP), and endothelial cells exposed to PP in the presence of ethanolic extract ofPunica granatum(PP + PG) at the following three doses: 14; 28; and 56 ppm. The expression of AT1-R was observed by immunohistochemistry technique, and thromboxane B2 level was done by immunoassay technique. Plasma from PP significantly increased AT1-R expression and thromboxane B2 levels compared to cells treated by normal pregnancy plasma. The increasing of AT1-R expression significantly (P<0.05) attenuated by high dose treatments ofPunica granatumextract. Moreover, the increasing of thromboxane B2 levels significantly (P<0.05) attenuated by lowest dose treatments ofPunica granatumextract. We further concluded thatPunica granatumfruit protects and inhibits the sensitivity of endothelial cells to plasma from preeclamptic patients due to inhibition of AT1-R expression (56 ppm) and reduced thromboxane B2 levels (14 ppm).

Investigation of antiproliferative effects of gossypin on lung cancer cell line

2021 ◽  
pp. 37-40
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Anticancer Agents ◽  
A549 Cells ◽  
Supportive Therapy ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
Lung Cancer Cell Line ◽  
Cancer Treatments ◽  
Mtt Method

Purpose: The rapid growth, morbidity and mortality of lung cancer and the lack of effective treatment have attracted great interest from researchers to find new cancer treatments aimed at the effect of gossypine on cell proliferation and apoptosis of A549 cells. The most used of these products are flavonoids. Gossypin is a potential chemo preventive and therapeutic agent for lung cancer. Material and Method: We investigated the effect of Gossypin anticancer activity on A549 cell proliferation with MTT method, depending on dose and time. In addition, mRNA expression levels of the apoptotic markers caspase-3 (CAS-3) and caspase-9 (CAS-9) were investigated by real-time PCR. In our study, six groups were used as control, gossypin (10, 20, 40 μM), cisplatin 5 μg/mL and cisplatin 5 μg/mL+gossypin 40 μM combine concentrations. The proliferative and antiapoptotic effects of gossypin at 24, 48 and 72 hours were investigated. Results were analyzed and presented as cell viability (%). Results: In our results, it was determined that gossypin especially at a dose of 40 μM and at 72 hours showed almost as much effect on A549 cells, but the highest inhibitory effect was seen in the 40 combined group of cisplatin 5 μg / mL + gossypin. In addition, gossypin caused a significant increase in apoptosis genes (CASP-3, CASP-9) compared to control. Conclusion: Our study showed that gossypin significantly increases the chemosensitivity of cisplatin. Based on this, it is predicted that gossypin can be used as a supportive therapy that increases the effectiveness of anticancer agents. However, more detailed research should be done for this.

Effects of antibiotics on the development and intestinal bacterial diversity of black soldier fly larvae

2021 ◽  
pp. 1-14
Author(s):  
J.B. Zhang ◽  
Y. Meng ◽  
J. Xu ◽  
C. Rensing ◽  
D. Wang
Keyword(s):  
Bacterial Diversity ◽  
Larval Growth ◽  
Anaerobic Bacteria ◽  
Inhibitory Effect ◽  
High Dose ◽  
Streptomycin Sulphate ◽  
Black Soldier Fly ◽  
Operational Taxonomic Units ◽  
Black Soldier Fly Larvae ◽  
Hermetia Illucens Larvae

The effects of four antibiotics (metronidazole (M) levofloxacin (L), sodium ampicillin (A), and streptomycin sulphate (S)) and their pair-wise combinations at three doses on the development and intestinal bacterial diversity of the black soldier fly (BSF; Hermetia illucens) larvae were studied. At a low dose M and L were able to inhibit larval growth. At a high dose, all antibiotics were shown to inhibit larval growth. However, the pair-wise combinational use of the antibiotics did not effectively enhance the inhibitory effect. The gut bacterial diversity of the normal control (NC) was significantly higher than the antibiotic-treated groups with 737 operational taxonomic units (OTUs) from the larval guts of NC, compared to 305 and 227 from ML and AS. The number of anaerobic bacteria in ML was significantly lower than in NC and AS, with the relative abundance of OTUs from larval guts of ML being only about 0.01, compared to 0.4 for NC and 0.15 for AS. These results indicated that antibiotics at the experimental concentration did not affect the palatability of food for insects, but they would affect the diversity of food and intestinal microorganisms of BSF larvae, and the inhibitory effect of antibiotics on growth and development of BSF larvae displayed in this study was a complex effect.

scholarly journals Culture cells in a model of microgravity

2017 ◽  
Vol 1 (1) ◽  
pp. 93-94
Author(s):  
Margarita Khotyanovich Dosina
Keyword(s):  
Human Fibroblasts ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
State Change ◽  
Rat Glioma ◽  
Full Strength ◽  
Culture Cells ◽  
Microgravity Simulation ◽  
Apoptosis And Necrosis ◽  
Flow Cytofluorimetry

Abstract The main objective of the work was to clarify the question - how will cell cultures functional state change after microgravity simulation when the shift in full strength direction takes place? Proliferation processes and apoptosis intensity in cell lines of rat glioma and human fibroblasts were compared in changing the position of flasks with cell culture in relation to the horizon. The detection of apoptosis and necrosis processes was carried out using flow cytofluorimetry. It was found that the change in full strength direction provides an inhibitory effect on tumor glial cells and fibroblasts’ proliferative activity enhances along with inhibition of apoptotic processes. Intensification of apoptotic processes in glioma cells and attenuation of cell death processes in normal cells - fibroblasts - are the result of cell cooperation disturbance.

scholarly journals AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3289
Author(s):  
Mi-Jeong Kim ◽  
Yoon Min ◽  
Juhee Son ◽  
Ji Young Kim ◽  
Ji Su Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Serum Starvation ◽  
Lung Cancers ◽  
Cancer Migration ◽  
Expression Of Genes ◽  
Autophagy Induction ◽  
Signaling Axis

TRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (AMPKα1, PRKAA1) is positively involved in autophagy induction and cancer progression by regulating TRAF6-BECN1 signaling axis. Mechanistically, AMPKα1 interacted with TRAF6 and BECN1. It also enhanced ubiquitination of BECN1 and autophagy induction. AMPKα1-knockout (AMPKα1KO) HEK293T or AMPKα1-knockdown (AMPKα1KD) THP-1 cells showed impaired autophagy induced by serum starvation or TLR4 (Toll-like receptor 4) stimulation. Additionally, AMPKα1KD THP-1 cells showed decreases of autophagy-related and autophagosome-related genes induced by TLR4. AMPKα1KO A549 cells exhibited attenuation of cancer migration and invasion induced by TLR4. Moreover, primary non-small cell lung cancers (NSCLCs, n = 6) with low AMPKαl levels showed markedly decreased expression of genes related to autophagy, cell migration and adhesion/metastasis, inflammation, and TLRs whereas these genes were significantly upregulated in NSCLCs (n = 5) with high AMPKαl levels. Consistently, attenuation of cancer migration and invasion could be observed in AMPKα1KO MDA-MB-231 and AMPKα1KO MCF-7 human breast cancer cells. These results suggest that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction.

Sign in / Sign up

Export Citation Format

Share Document