scholarly journals Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 476
Author(s):  
Bundit Promraksa ◽  
Praewpan Katrun ◽  
Jutarop Phetcharaburanin ◽  
Yingpinyapat Kittirat ◽  
Nisana Namwat ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Defense Mechanism ◽  
Tricarboxylic Acid Cycle ◽  
Complex Structure ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Coniferyl Alcohol ◽  
Metabolic Changes ◽  
Control Group ◽  
Scoparia Dulcis

Cholangiocarcinoma (CCA) is a major cause of mortality in Northeast Thailand with about 14,000 deaths each year. There is an urgent necessity for novel drug discovery to increase effective treatment possibilities. A recent study reported that lignin derived from Scoparia dulcis can cause CCA cell inhibition. However, there is no evidence on the inhibitory effect of coniferyl alcohol (CA), which is recognized as a major monolignol-monomer forming a very complex structure of lignin. Therefore, we aimed to investigate the effect of CA on CCA cell apoptosis. We demonstrated that a half-inhibitory concentration of CA on KKU-100 cells at 48 h and 72 h was 361.87 ± 30.58 and 268.27 ± 18.61 μg/mL, respectively, and on KKU-213 cells 184.37 ± 11.15 and 151.03 ± 24.99 μg/mL, respectively. Furthermore, CA induced CCA cell apoptosis as demonstrated by annexin V/PI staining in correspondence with an increase in the BAX/Bcl-2 ratio. A metabonomic study indicated that CA significantly decreased the intracellular concentrations of glutathione and succinate in KKU-213 cells and increased dihydrogen acetone phosphate levels in KKU-100 cells treated with 200 µg/mL of CA compared to the control group. In conclusion, CA induced cellular metabolic changes which are involved in the antioxidant defense mechanism, glycerophospholipid metabolism and the tricarboxylic acid cycle. CA may serve as a potent anticancer agent for CCA treatment by inducing CCA cellular apoptosis.

Studies on Apoptosis and Mechanism of Curcumin Chitosan Induced Human Colon Cancer Cells in Colorectal Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 987-991
Author(s):  
Quanlan Wang ◽  
Peng Liao ◽  
Yinglin Wu ◽  
Yuanhua Huang ◽  
Yan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Annexin V ◽  
Human Colon ◽  
Optical Microscope ◽  
Inhibitory Effect ◽  
Control Group ◽  
Dependent Manner ◽  
Human Colon Cancer ◽  
Ht29 Cells

To explore the function of curcumin chitosan on the proliferation of human colorectal cancer HT29 cells and to explore its effect on apoptosis. We applied MTT assay to test the inhibitory effect of curcumin chitosan on the proliferation of HT29 cells. The alterations of colorectal cancer cell morphology were observed by optical microscope and electron microscope. The change of early apoptosis rate was determined by flow cytometry using Annexin-V/PI double staining. By Comparison with the control group, curcumin chitosan significantly suppressed the cell proliferation and promoted cell apoptosis of HT29 cells in not only dose- but also time-dependent manner; through light microscopy and electron microscopy, the cell volume was reduced, the cell membrane was shrunk, chromatin was significantly concentrated. Typical apoptotic features such as aggregation; flow cytometry confirmed a significant increase in apoptotic rates (p < 0 05).

Downregulation of microRNA-586 Inhibits Proliferation, Invasion and Metastasis and Promotes Apoptosis in Human Osteosarcoma U2-OS Cell Line

2015 ◽  
Vol 146 (4) ◽  
pp. 268-278 ◽  
Author(s):  
Lei Yang ◽  
Zong-Ming Liu ◽  
Yan-Wei Rao ◽  
Shao-Qian Cui ◽  
Huan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Cell Number ◽  
Cell Counting ◽  
Control Group ◽  
Cell Cycle Distribution ◽  
Invasion And Metastasis ◽  
Blank Group ◽  
Group Control Group

In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis.

scholarly journals Effects of Holothurian Glycosaminoglycan on the Sensitivity of Lung Cancer to Chemotherapy

2020 ◽  
Vol 19 ◽  
pp. 153473542091143
Author(s):  
Cunzhi Lin ◽  
Xinhong Zhu ◽  
Qing Jin ◽  
Aihua Sui ◽  
Jinfeng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Sea Cucumber ◽  
Caspase 3 ◽  
A549 Cells ◽  
Annexin V ◽  
Inhibitory Effect ◽  
The Body ◽  
Control Group ◽  
Apoptosis Pathway

Sea cucumber is a kind of food. Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber. Administration of hGAG and cisplatin (DDP) together to treat lung cancer was investigated. Lung adenocarcinoma A549 cells were cultured and divided into 4 groups: control group, hGAG 100 µg/mL group, DDP 3 µg/mL group, and hGAG 100 µg/mL + DDP 3 µg/mL group. Cell inhibition and apoptosis was evaluated by CCK8 and Hoechst33258 staining. Cell cycle was tested by Annexin V-FITC/PI (propidium iodide) double-staining and flow cytometry. The expression of mRNA and protein of Bcl-2, Bax, caspase-3, and survivin were detected by reverse transcriptase-polymerase chain reaction and Western blot, respectively. The results showed that hGAG combined with DDP enhanced the inhibitory effect of DDP on A549 lung cells through apoptosis pathway. The mechanism of apoptosis may be related to the reduction of Bcl-2 and survivin, as well as the ascension of Bax and caspase-3. hGAG could promote A549 cell cycle arrest in G1 and G2 phase and improve the DDP chemotherapy effects on A549 cells.

scholarly journals Isoimperatorin Induces Apoptosis of Nasopharyngeal Carcinoma Cells via the MAPK/ERK1/2 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jie Liu ◽  
Lan He ◽  
Jing Hu ◽  
Kairui Li ◽  
Fangliang Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Related Protein ◽  
Cellular Analysis ◽  
Cne2 Cell ◽  
Proapoptotic Protein

Objective. To investigate the effect of isoimperatorin on nasopharyngeal carcinoma CNE2 cell apoptosis and the role of the MAPK/ERK1/2 signaling pathway in inducing apoptosis. Methods. Real-time cellular analysis technology (RTCA) and MTT were used to detect cell proliferation; Annexin V-FITC/PI dual-fluorescence flow cytometry analysis, Hoechst 33342 staining, and mitochondrial membrane potential detection kit were used to detect cell apoptosis; western blot was used to detect protein expression. Results. Different concentrations of isoimperatorin (10 μM, 20 μM, 30 μM, and 40 μM) significantly inhibited the nasopharyngeal carcinoma CNE2 cell proliferation, and 48 h later, the inhibitory effect of the 40 μM treatment was significantly higher than that of 10 μM and 20 μM. Treatment for 48 h significantly induced nasopharyngeal carcinoma cell apoptosis and resulted in nuclear pyknosis and fragmentation. At the same timepoint, the expression levels of proliferation-related protein PCNA as well as antiapoptosis proteins XIAP, survivin, and Bcl-2 were decreased by drug treatment, the expression level of proapoptosis protein Bax was increased, and the expression of the key MAPK/ERK1/2 signaling pathway proteins p-c-Raf, p-MEK, and p-ERK1/2 of were decreased. After activation of the MAPK/ERK1/2 signaling pathway by isoprenaline hydrochloride (ISO), the efficacy of isoimperatorin to downregulate p-c-Raf, p-MEK, and p-ERK1/2 expressions in the MAPK/ERK1/2 signaling pathway and proliferation-related protein PCNA as well as antiapoptosis proteins XIAP, surviving, and Bcl-2 was reduced compared with that of isoimperatorin alone, the effect of upregulating the proapoptotic protein Bax was reduced, and the apoptosis rate was also decreased. Conclusion. Isoimperatorin can induce nasopharyngeal carcinoma CNE2 cell apoptosis through the MAPK/ERK1/2 signaling pathway.

1H-NMR-based metabonomic analysis of metabolic profiling in diabetic nephropathy rats induced by streptozotocin

2011 ◽  
Vol 300 (4) ◽  
pp. F947-F956 ◽  
Author(s):  
Liangcai Zhao ◽  
Hongchang Gao ◽  
Fulin Lian ◽  
Xia Liu ◽  
Yongxiang Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Metabolic Profiling ◽  
Ketone Body ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Metabolic Changes ◽  
Control Group ◽  
Acid Cycle ◽  
Pattern Recognition Analysis ◽  
Pathogenic Process

Elucidation of the metabolic profiling in diabetic nephropathy (DN) rats is of great assistance for understanding the pathogenesis of DN. In this study, 1H-nuclear magnetic resonance (NMR)-based metabonomics combined with HPLC measurements was used to quantitatively analyze the metabolic changes in urine and kidney extracts from diabetic 2-wk and 8-wk rats induced by streptozotocin (STZ). Pattern recognition analysis of either urine or kidney extracts indicated that the two diabetic groups were separated obviously from the control group, suggesting that the metabolic profiles of the diabetic groups were markedly different from the control. The diabetic 8-wk rats showed lower levels of creatine, dimethylamine, and higher levels of ascorbate, succinate, lactate, citrate, allantoin, 2-ketoglutarate, and 3-hydrobutyrate (3-HB) in the urine samples. Moreover, the diabetic 8-wk rats displayed lower levels of succinate, creatine, myo-inositol, alanine, lactate, and ATP, and higher levels of 3-HB and glucose in the kidney extracts. The observed metabolic changes imply the enhanced pathways of either lipid or ketone body synthesis and decreased pathways of either tricarboxylic acid cycle or glycolysis in DN rats compared with the control. Our results suggest that the energy metabolic changes are associated with the pathogenic process of DN.

The Effects of Heparin and Annexin V on Fibrin Accretion after Injury in the Jugular Veins of Rabbits

1993 ◽  
Vol 69 (03) ◽  
pp. 227-230 ◽  
Author(s):  
J Van Ryn-McKenna ◽  
H Merk ◽  
T H Müller ◽  
M R Buchanan ◽  
W G Eisert
Keyword(s):  
Vessel Wall ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Specific Effect ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Jugular Veins ◽  
Prothrombinase Complex ◽  
Wall Injury

SummaryWe compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re-established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely deendothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham-operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p <0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins. We conclude that, i) mild vessel wall injury (selective de-endothelialization) in veins results in a thrombogenic vessel wall; ii) the thrombogenecity of which is not inhibited by prophylactic doses of heparin; but iii) is inhibited by annexin V, which binds to injured vessel wall surface, and inhibits thrombin generation independently of antithrombin III.

Effects of oestradiol benzoate (OeB) and human chorionic gonadotrophin (hCG) on the testes and accessory sex glands of the rat

1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger
Keyword(s):  
Treated Group ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Control Group ◽  
Intact Male ◽  
Intact Control ◽  
Testosterone Levels ◽  
Oestradiol Benzoate ◽  
Direct Inhibitory Effect

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

Ruxolitinib Regulates the Autophagy Machinery in Multiple Myeloma Cells

2020 ◽  
Vol 20 (18) ◽  
pp. 2316-2323 ◽  
Author(s):  
Alican Kusoglu ◽  
Bakiye G. Bagca ◽  
Neslihan P.O. Ay ◽  
Guray Saydam ◽  
Cigir B. Avci
Keyword(s):  
Multiple Myeloma ◽  
Cell Line ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Annexin V ◽  
Myeloma Cell ◽  
Control Group ◽  
Multiple Myeloma Cell ◽  
Ic50 Values ◽  
Stat Pathway

Background: Ruxolitinib is a selective JAK1/2 inhibitor approved by the FDA for myelofibrosis in 2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for haematological malignancies are on the rise. In multiple myeloma which is a cancer of plasma cells, the Interleukin- 6/JAK/STAT pathway is emerging as a therapeutic target since the overactivation of the pathway is associated with poor prognosis. Objective: In this study, our purpose was to discover the potential anticancer effects of ruxolitinib in ARH-77 multiple myeloma cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Methods: Cytotoxic effects of ruxolitinib in ARH-77 and NCI-BL 2171 cells were determined via WST-1 assay. The autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation was investigated. Apoptotic effects of ruxolitinib were analyzed with Annexin V-FITC Detection Kit and flow cytometry. We performed RT-qPCR to demonstrate the expression changes of the genes in the IL-6/JAK/STAT pathway in ARH-77 and NCI-BL 2171 cells treated with ruxolitinib. Results: We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9μM at the 72nd hour, respectively. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70 folds in ARH-77 and NCI-BL 2171 cells compared to the control group, respectively. Treatment with ruxolitinib decreased the expressions of IL-6, IL-18, JAK2, TYK2, and AKT genes, which play significant roles in MM pathogenesis. Conclusion: All in all, ruxolitinib is a promising agent for the regulation of the IL-6/JAK/STAT pathway and interferes with the autophagy mechanism in MM.

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