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

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20040955 ◽

2019 ◽

Vol 20 (4) ◽

pp. 955 ◽

Cited By ~ 1

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.

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

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i9.20500 ◽

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.

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Antiproliferative and Apoptotic Properties of Andrographolide Against Human Colon Cancer DLD1 Cell Line

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666191125111920 ◽

2020 ◽

Vol 20 (6) ◽

pp. 930-942 ◽

Cited By ~ 1

Author(s):

Imran Khan ◽

Sadaf Mahfooz ◽

Irfan A. Ansari

Keyword(s):

Colon Cancer ◽

Cell Line ◽

Mtt Assay ◽

Caspase 3 ◽

Chemotherapeutic Agents ◽

Synergistic Activity ◽

Dependent Manner ◽

Apoptosis Induction ◽

Dld1 Cell ◽

Activation Assay

Background: In recent years, natural products have received great attention for cancer prevention owing to their various health benefits, noticeable lack of toxicity and side effects, and the limitations of chemotherapeutic agents. Andrographolide, a labdane diterpenoid is a principal bioactive constituent of Andrographis paniculata Nees, exhibits significant anticancer activity. Objective: The efficacy of andrographolide on colon cancer cells is yet to be elucidated completely. Therefore, we investigated the anticancer efficiency of andrographolide in colon cancer DLD1 cell line. Methods: Antiproliferative activity of andrographolide on DLD1 cells was evaluated by MTT assay, LDH release assay, morphological analysis and colony formation assay. Induction of apoptosis was determined by DAPI staining, Annexin V-FITC staining assay, and caspase-3 activation assay. Role of andrographolide induced cellular reactive oxygen species (ROS) and its association with apoptosis induction in DLD1 cells was elucidated by DCFDA dye. Synergistic ability of andrographolide with 5- fluorouracil (5-FU) and paclitaxel (PTX) was evaluated by MTT assay. Results: Results of the present study indicated that andrographolide declined cell viability of DLD1 cells in a concentration and time-dependent manner. Andrographolide induced apoptosis via nuclear condensation, phosphatidylserine externalization and caspase-3 activation. It also augmented cellular ROS levels which were in turn associated with apoptosis induction in DLD1 cells. Moreover, andrographolide displayed synergistic activity with 5-FU and PTX against DLD1 cells. Conclusion: The present study showed that andrographolide demonstrated antiproliferative and apoptotic properties, moreover it also displayed synergistic effect with chemotherapeutic drugs in colon cancer DLD1 cells.

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Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

Cancer Cell International ◽

10.1186/s12935-021-01942-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dongxiao Jiang ◽

Shufei Ding ◽

Zhujun Mao ◽

Liyan You ◽

Yeping Ruan

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Caspase 3 ◽

Time Dependent ◽

Integrated Analysis ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Dapi Staining ◽

Aloe Emodin

Abstract Background Colon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic. Methods We identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells. Results The MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria. Conclusion These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

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Dual inhibition of COX-2/5-LOX blocks colon cancer proliferation, migration and invasion in vitro

Oncology Reports ◽

10.3892/or.2015.4506 ◽

2015 ◽

Vol 35 (3) ◽

pp. 1680-1688 ◽

Cited By ~ 17

Author(s):

XIAO-HANG CHE ◽

CHUN-LIN CHEN ◽

XIAO-LEI YE ◽

GUO-BIN WENG ◽

XIAN-ZHI GUO ◽

...

Keyword(s):

Colon Cancer ◽

Migration And Invasion ◽

Cancer Proliferation ◽

Dual Inhibition ◽

Cox 2

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Cox-2 inhibition for the treatment of colon cancer

International Journal of Cancer ◽

10.1002/ijc.20071 ◽

2004 ◽

Vol 110 (2) ◽

pp. 310-310

Author(s):

Carlos Becerra

Keyword(s):

Colon Cancer ◽

Cox 2

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Smad3 mutant mice develop colon cancer with overexpression of COX-2

Oncology Letters ◽

10.3892/ol.2017.5639 ◽

2017 ◽

Vol 13 (3) ◽

pp. 1535-1538 ◽

Cited By ~ 1

Author(s):

Yu-Ping Zhu ◽

Zhuo Liu ◽

Zhi-Xuan Fu ◽

De-Chuan Li

Keyword(s):

Colon Cancer ◽

Mutant Mice ◽

Cox 2

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Epidermal growth factor receptor transactivation is required for proteinase-activated receptor-2-induced COX-2 expression in intestinal epithelial cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00358.2011 ◽

2012 ◽

Vol 303 (1) ◽

pp. G111-G119 ◽

Cited By ~ 17

Author(s):

Christina L. Hirota ◽

France Moreau ◽

Vadim Iablokov ◽

Michael Dicay ◽

Bernard Renaux ◽

...

Keyword(s):

Colon Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Intestinal Epithelial Cells ◽

Growth Factor Receptor ◽

Intestinal Epithelial ◽

Kinase Signaling ◽

Epidermal Growth ◽

Cox 2

Proteinase-activated receptor (PAR)2, a G protein-coupled receptor activated by serine proteinases, has been implicated in both intestinal inflammation and epithelial proliferation. Cyclooxygenase (COX)-2 is overexpressed in the gut during inflammation as well as in colon cancer. We hypothesized that PAR2 drives COX-2 expression in intestinal epithelial cells. Treatment of Caco-2 colon cancer cells with the PAR2-activating peptide 2-furoyl-LIGRLO-NH2 (2fLI), but not by its reverse-sequence PAR2-inactive peptide, for 3 h led to an increase in intracellular COX-2 protein expression accompanied by a COX-2-dependent increase in prostaglandin E2 production. 2fLI treatment for 30 min significantly increased metalloproteinase activity in the culture supernatant. Increased epidermal growth factor receptor (EGFR) phosphorylation was observed in cell lysates following 40 min of treatment with 2fLI. The broad-spectrum metalloproteinase inhibitor marimastat inhibited both COX-2 expression and EGFR phosphorylation. The EGFR tyrosine kinase inhibitor PD153035 also abolished 2fLI-induced COX-2 expression. Although PAR2 activation increased ERK MAPK phosphorylation, neither ERK pathway inhibitors nor a p38 MAPK inhibitor affected 2fLI-induced COX-2 expression. However, inhibition of either Src tyrosine kinase signaling by PP2, Rho kinase signaling by Y27632, or phosphatidylinositol 3 (PI3) kinase signaling by LY294002 prevented 2fLI-induced COX-2 expression. Trypsin increased COX-2 expression through PAR2 in Caco-2 cells and in an EGFR-dependent manner in the noncancerous intestinal epithelial cell-6 cell line. In conclusion, PAR2 activation drives COX-2 expression in Caco-2 cells via metalloproteinase-dependent EGFR transactivation and activation of Src, Rho, and PI3 kinase signaling. Our findings provide a mechanism whereby PAR2 can participate in the progression from chronic inflammation to cancer in the intestine.

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