scholarly journals IN SILICO DOCKING STUDIES ON KAEMPFERITRIN WITH DIVERSE INFLAMMATORY AND APOPTOTIC PROTEINS FUNCTIONAL APPROACH TOWARDS THE COLON CANCER

2017 ◽  
Vol 9 (9) ◽  
pp. 199
Author(s):  
Mydhili Govindarasu ◽  
Mariyappan Palani ◽  
Manju Vaiyapuri
Keyword(s):  
Colon Cancer ◽  
Cytochrome P450 ◽  
Amino Acid ◽  
Protein Kinase ◽  
Caspase 3 ◽  
Tnf Α ◽  
Different Types ◽  
Inflammatory Proteins ◽  
Cox 2 ◽  
Apoptotic Proteins

Objective: The objective of this research was to formulate the binding energies and interaction of amino acid residues in kaempferitrin with different types of apoptotic and inflammatory proteins of colon cancer.Methods: AutoDock Vina and MGL tool were used for docking calculations. Both programs require the pdbqt input files and allow for flexibility of all the torsional bonds of small molecules. Discovery Studio Visualizer v3.5 was used for removal of water molecules and ligands and the pymol program was used to do analysis of the docking with various apoptotic proteins BAX, Bcl-2, COX-2, Protein kinase B.Results: In our study was developed binding energy scoring function of kaempferitrin docked with different types of inflammatory proteins and apoptotic proteins. Binding score values for-6.9 (BAX),-7.2 (Bcl-2),-7.3 (caspase-3),-8.8 (Cox-2),-7.4 (Cytochrome P450),-6.7 (Proteinase kinase B),-8.0 (TNF-α) and-7.2 (VEGF) kcal/mol, respectively. Amino acid interaction of kaempferitrin with proteins for ARG-25, LEU-52, ASN-54, PHE-55, GLU-17, LYS-14, TRP-22, THR-21 GLY-16 (Protein Kinase B), ASP-102, ASN-48, GLN-52, ASP-104 (BAX), GLU-176, TRP-173, GLU-132, PHE-135 (Bcl-2), SER-249, ASP-2, ASN-208, GLN-217, LEU-242 (Caspase 3), TYR-55, HIS-39, SER-49, GLU-322, GLY-326 (COX-2), SER-95, LEU-94, ARG-82, VAL-123, ALA-96 (TNF-α), ASP-414, LYS-322, GLU-326, GLU-416, GLU-438, ALA-439, GLU-437 (Cytochrome P450) and LEU-47, GLN-46, CYS-61, CYS-60, ASP-63, GLU-67, GLY-65, LEU-66 (VEGF) respectively.Conclusion: The results obtained in this research work clearly indicated the docking scores of apoptotic and Inflammatory proteins imply that kaempferitrin is an effective inhibitory compound for colon cancer.

scholarly journals Amino acid sequences characterization and anti-inflammatory potency evaluation of Portulaca oleracea L. oligopeptides in macrophages

RSC Advances ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 7321-7327
Author(s):  
Shihui Chang ◽  
Liping Wang ◽  
Ting Zhang ◽  
Yan Nie ◽  
Ruijie Liu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Amino Acid Sequences ◽  
Portulaca Oleracea ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

POP-1 performed excellent anti-inflammatory potency by attenuating the pro-inflammatory cytokine expression (TNF-α, NO, IL-1β); inhibiting iNOS and COX-2 expressions and regulating the MAPK, PI3K/Akt and NF-κB signaling pathways.

scholarly journals Modulation of COX-2 and NADPH oxidase-4 by Alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats.

2021 ◽  
Author(s):  
Mona Elhadidy ◽  
Ahlam Elmasry ◽  
Hassan Reda Hassan Elsayed ◽  
Mohammad H El-Nablaway ◽  
Shereen Hamed ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lipoic Acid ◽  
Caspase 3 ◽  
Smooth Muscle Actin ◽  
Male Rats ◽  
Nadph Oxidase 4 ◽  
Tnf Α ◽  
Cox 2 ◽  
Index Ratio ◽  
Sirius Red

Abstract purpose: Busulfan is an antineoplastic drug that produces pulmonary fibrosis. This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.Methods: Twenty-four adult male rats were divided into four groups: control, α-lipoic acid (ALA), busulfan, and busulfan plus α-lipoic acid. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA were assessed using qRT-PCR.Results: administration of ALA significantly ameliorated BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.Conclusion: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

scholarly journals Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Saima Khatoon ◽  
Nidhi Bharal Agarwal ◽  
Mohammed Samim ◽  
Ozair Alam
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Seizure Threshold ◽  
Experimental Epilepsy ◽  
Kindling Model ◽  
Histological Alterations ◽  
Tnf Α ◽  
Cox 2

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.

Protective Effect of Nerium Oleander Distillate and Tarantula Cubensis Alcoholic Extract on Cancer Biomarkers on Colon and Liver Tissues of Rats with Experimental Colon Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Burak Dik ◽  
Devran Coskun ◽  
Ayşe Er
Keyword(s):  
Colon Cancer ◽  
Caspase 3 ◽  
Cancer Biomarkers ◽  
Nerium Oleander ◽  
Control Group ◽  
Alcoholic Extract ◽  
Colon Cancers ◽  
Cancer Types ◽  
Cox 2 ◽  
Liver Tissues

Background: Colon cancers are among the three major cancer types that result in death. The research for effective treatment continues. Objective: The aim of this study is to determine the effects of Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander (NO) distillate on the levels of midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase 3 in liver and colon tissues of experimentally induced colon cancer in rats. Method: The liver and colon tissues of the rats were divided into Control, Colon Cancer (AZM), AZM+TCAE and AZM+NO groups and they were homogenized. The levels of midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase 3 in the colon and liver tissues were measured by ELISA kits. Results: All parameters levels of colon and liver tissues in the AZM group were generally higher (p<0.05) than the Control group. TCAE and NO prevented (p<0.05) the increases in midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase-3 levels in the colon. NO prevented increase of all parameters except for IGF level, while TCAE prevented (p<0.05) the increase of all values apart from COX-2 and IGF levels in the liver. Conclusion: NO and TCAE may prevented at the specified marker levels of colon in the AZM induced colon cancer. The increases the level of parameters in the liver are not as severe as in the colon, due to the 18-week study period may not be sufficient for liver metastasis formationIn the future molecular studies should be done to determine the mechanisms and pathways of them more clearly.

Sodium Butyrate Induces Human Colon Carcinoma HT-29 Cell Apoptosis through a Mitochondrial Pathway

2009 ◽  
Vol 37 (3) ◽  
pp. 803-811 ◽  
Author(s):  
L Wang ◽  
H-S Luo ◽  
H Xia
Keyword(s):  
Colon Cancer ◽  
Sodium Butyrate ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Human Colon ◽  
Caspase 9 ◽  
Human Colon Cancer ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ht 29

Some tumours respond favourably to tumour necrosis factor-alpha (TNF-α). Despite this preferential sensitivity, resistance to TNF-α remains a clinical problem and more interest is now being focused on finding compounds that induce apoptosis through other pathways. Sodium butyrate (NaBt) has anti-tumour effects on colon cancer cells, inhibiting cell growth and promoting differentiation and apoptosis. In this study we investigated whether NaBt induced apoptosis in the human colon cancer cell line HT-29 and examined the intracellular mechanisms involved. Pre-incubation of cells with NaBt significantly increased apoptosis as measured by fluorescence activated cell sorter analysis and mitochondrial membrane potential determination. This effect could be blocked with the caspase inhibitors, z-VAD-fmk (pan-caspase inhibitor), z-DEVD-fmk (caspase-3 inhibitor) and z-LEHD-fmk (caspase-9 inhibitor), but not with z-IETD-fmk (caspase-8 inhibitor). Enhancement of caspase-3 and caspase-9 activities suggests that NaBt induces apoptosis via mitochondrial pathways not involving TNF-α.

scholarly journals KMU-1170, a Novel Multi-Protein Kinase Inhibitor, Suppresses Inflammatory Signal Transduction in THP-1 Cells and Human Osteoarthritic Fibroblast-Like Synoviocytes by Suppressing Activation of NF-κB and NLRP3 Inflammasome Signaling Pathway

2021 ◽  
Vol 22 (3) ◽  
pp. 1194
Author(s):  
Hye Suk Baek ◽  
Victor Sukbong Hong ◽  
Sang Hyon Kim ◽  
Jinho Lee ◽  
Shin Kim
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Nlrp3 Inflammasome ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Tnf Α ◽  
Cox 2 ◽  
Fibroblast Like Synoviocytes

Protein kinases regulate protein phosphorylation, which are involved in fundamental cellular processes such as inflammatory response. In this study, we discovered a novel multi-protein kinase inhibitor, KMU-1170, a derivative of indolin-2-one, and investigated the mechanisms of its inflammation-inhibiting signaling in both THP-1 cells and human osteoarthritic fibroblast-like synoviocytes (FLS). We demonstrated that in THP-1 cells, KMU-1170 inhibited lipopolysaccharide (LPS)-induced upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and, furthermore, suppressed LPS-induced phosphorylation of transforming growth factor-β-activated kinase 1, JNK, ERK, inhibitor of NF-κB kinase α/β (IKKα/β), and NF-κB p65 as well as nuclear translocation of NF-κB p65. Moreover, KMU-1170 suppressed LPS-induced upregulation of proinflammatory cytokines such as IL-1β, TNF-α, and IL-6, and, notably, inhibited LPS-induced upregulation of the NLRP3 inflammasome in THP-1 cells. Importantly, KMU-1170 attenuated LPS-mediated inflammatory responses in human osteoarthritic FLS, such as the upregulation of IL-1β, TNF-α, IL-6, iNOS, and COX-2 and the phosphorylation of IKKα/β and NF-κB p65. Collectively, these results suggest that KMU-1170 inhibits inflammatory signal transduction and could be developed as a potential anti-inflammatory agent.

scholarly journals Cyclooxygenase-2 Regulation in Colon Cancer Cells

2005 ◽  
Vol 280 (16) ◽  
pp. 15503-15509 ◽  
Author(s):  
Xin Tong ◽  
Lei Yin ◽  
Shree Joshi ◽  
Daniel W. Rosenberg ◽  
Charles Giardina
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Cancer Cell Line ◽  
Cyclooxygenase 2 ◽  
Pharmacological Intervention ◽  
Colon Cancer Cells ◽  
Tnf Α ◽  
Cox 2

We are interested in the mechanism of cyclooxygenase-2 (Cox-2) regulation in colon cancer cells because this knowledge could provide insight into colon carcinogenesis and suggest ways to suppress Cox-2 expression in colon tumors. Studying the HT-29 colon cancer cell line as a model, we found that Cox-2 mRNA and protein levels were activated over 10-fold by the inflammatory cytokine tumor necrosis factor (TNF)-α. Moreover, we found that the histone deacetylase inhibitors butyrate and trichostatin A could block Cox-2 activation in a gene-specific manner. TNF-α and butyrate did not significantly affect Cox-2 promoter activity, mRNA stability, or negative regulation by the Cox-2 3′-untranslated RNA region. A nuclear run-on assay showed that TNF-α increased Cox-2 transcription, whereas butyrate was suppressive. Because butyrate has been reported to suppress polymerase elongation on the c-mycgene, we employed the chromatin immunoprecipitation assay to determine the influence of butyrate and trichostatin A on polymerase distribution on the Cox-2 gene. These data indicated that butyrate restricted polymerase elongation from exon 1 to 2 on both the c-mycand Cox-2 genes. We propose that histone deacetylases regulate a transcriptional block on the Cox-2 and c-mycgenes and that this block may be a potential target for pharmacological intervention.

Negative correlation between caspase-3 and COX-2 expression in colon cancer

2012 ◽  
Vol 32 (1) ◽  
pp. 68-74
Author(s):  
Tahany M. Shams ◽  
Maha M. Atwa ◽  
Mohamed E. Shams
Keyword(s):  
Colon Cancer ◽  
Negative Correlation ◽  
Caspase 3 ◽  
Cox 2

scholarly journals The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 955 ◽  
Author(s):  
Kamila Środa-Pomianek ◽  
Krystyna Michalak ◽  
Anna Palko-Łabuz ◽  
Anna Uryga ◽  
Piotr Świątek ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Colon Cancer Cells ◽  
Phenothiazine Derivatives ◽  
Component Mixture ◽  
P Glycoprotein ◽  
Novel Approach ◽  
Combined Use ◽  
Cox 2

Since none of the multidrug resistance (MDR) modulators tested so far found their way into clinic, a novel approach to overcome the MDR of cancer cells has been proposed. The combined use of two MDR modulators of dissimilar mechanisms of action was suggested to benefit from the synergy between them. The effect of three phenothiazine derivatives that were used as single agents and in combination with simvastatin on cell growth, apoptosis induction, activity, and expression of cyclooxygenase-2 (COX-2) in doxorubicin-resistant colon cancer cells (LoVo/Dx) was investigated. Treatment of LoVo/Dx cells by phenothiazine derivatives combined with simvastatin resulted in an increase of doxorubicin cytotoxicity and its intracellular accumulation as compared to the treatment with phenothiazine derivatives that were used as single agents. Similarly, LoVo/Dx cells treated with two-component mixture of modulators showed the reduced expression of ABCB1 (P-glycoprotein) transporter and COX-2 enzyme, both on mRNA and protein level. Reduced expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax were also detected. Additionally, COX-2 activity was diminished, and caspase-3 activity was increased to a higher extent by phenothiazine derivative:simvastatin mixtures than by phenothiazine derivatives themselves. Therefore, the introduction of simvastatin strengthened the anti-MDR, anti-inflammatory, and pro-apoptotic properties of phenothiazines in LoVo/Dx cells.

The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer

2020 ◽  
Vol 98 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Saber Ghazizadeh Darband ◽  
Ehsan Saboory ◽  
Shirin Sadighparvar ◽  
Mojtaba Kaviani ◽  
Kazhal Mobaraki ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Exercise Program ◽  
Serum Levels ◽  
Aberrant Crypt Foci ◽  
Protective Effects ◽  
Histological Changes ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

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