scholarly journals AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Angelo Cerbone ◽  
Cristina Toaldo ◽  
Stefania Pizzimenti ◽  
Piergiorgio Pettazzoni ◽  
Chiara Dianzani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Combined Treatment ◽  
Colon Cancer Cells ◽  
Positive Interaction ◽  
Anti Inflammatory

PPARαs are nuclear receptors highly expressed in colon cells. They can be activated by the fibrates (clofibrate, ciprofibrate etc.) used to treat hyperlipidemia. Since PPARαtranscriptional activity can be negatively regulated by JNK, the inhibition of JNK activity could increase the effectiveness of PPARαligands. We analysed the effects of AS601245 (a JNK inhibitor) and clofibrate alone or in association, on proliferation, apoptosis, differentiation and the gene expression profile of CaCo-2 human colon cancer cells. Proliferation was inhibited in a dose-dependent way by clofibrate and AS601245. Combined treatment synergistically reduced cell proliferation, cyclin D1 and PCNA expression and induced apoptosis and differentiation. Reduction of cell proliferation, accompanied by the modulation of p21 expression was observed in HepG2 cells, also. Gene expression analysis revealed that some genes were highly modulated by the combined treatment and 28 genes containing PPRE were up-regulated, while clofibrate alone was ineffective. Moreover, STAT3 signalling was strongly reduced by combined treatment. After combined treatment, the binding of PPARαto PPRE increased and paralleled with the expression of the PPAR coactivator MED1. Results demonstrate that combined treatment increases the effectiveness of both compounds and suggest a positive interaction between PPARαligands and anti-inflammatory agents in humans.

Gene expression profile in colon cancer cells with respect to XIAP expression status

2008 ◽  
Vol 24 (3) ◽  
pp. 245-260 ◽  
Author(s):  
Liang Qiao ◽  
Gloria H. Y. Li ◽  
Yun Dai ◽  
Jide Wang ◽  
Zesong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Colon Cancer Cells ◽  
Xiap Expression ◽  
Expression Status

M1621 Gene Expression Profile in Colon Cancer Cells in Response to Troglitazone: Impact of XIAP Expression

2008 ◽  
Vol 134 (4) ◽  
pp. A-384
Author(s):  
Liang Qiao ◽  
Gloria HY Li ◽  
Yun Dai ◽  
Zesong Li ◽  
Bing Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Colon Cancer Cells ◽  
Xiap Expression

scholarly journals Inhibition of Stearoyl-CoA Desaturase-1 Activity Suppressed SREBP Signaling in Colon Cancer Cells and Their Spheroid Growth

2019 ◽  
Vol 1 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Xian-Yang Qin ◽  
Soichi Kojima
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cholesterol Metabolism ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Spheroid Growth ◽  
Stearoyl Coa Desaturase

Unsaturated fatty acids are critical in promoting colon tumorigenesis and its stemness. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipid desaturase associated with colon cancer cell proliferation and metastasis control. This study aims to evaluate the effects of SCD1 inhibition on colon cancer spheroid growth in a three-dimensional cell culture system. An analysis of clinical data showed that increased SCD1 gene expression in colon tumors was negatively correlated with the prognosis. A chemical inhibitor of SCD1, CAY10566, inhibited the growth of colon cancer cells in both monolayer and sphere cultures. In addition, oleic acid administration—a monounsaturated fatty acid generated by the action of SCD1—prevented the suppression of sphere formation by CAY10566. RNA-sequencing data from 382 colon tumor patient samples obtained from the Cancer Genome Atlas database showed that 806 genes were SCD1-associated genes in human colon cancer. Correlation analysis identified the master regulator of lipid homeostasis sterol regulatory element-binding protein 2 (SREBP2) as a prominent transcription factor, whose expression was positively correlated with SCD1 in human colon cancer. SCD1 knockdown using siRNA in colon cancer samples, suppressed SREBP2 gene expression, providing direct evidence that SREBP signaling is under the control of SCD1 in these cells. Pathway analysis in the Ingenuity Pathways Analysis platform showed that SCD1 expression positively correlated with genes involved in multiple pathways, including lipid synthesis and incorporation, cell proliferation, and tissue tumorigenesis. Further network analysis revealed a central role for Myc in the network hierarchy of the SCD1-correlated genes. These findings suggested that SCD1 inhibition would be an effective strategy for suppressing colon cancer spheroid growth, partly through downregulating SREBP-mediated lipid and cholesterol metabolism and Myc signaling.

scholarly journals Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hyun Joo Jang ◽  
Eun Mi Hong ◽  
Juah Jang ◽  
Jung Eun Choi ◽  
Se Woo Park ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Combined Treatment ◽  
Molar Ratio ◽  
Colon Cancer Cells ◽  
Activity Assay ◽  
Ht 29

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan.Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance.Results. The IC50values of simvastatin alone and irinotecan alone were115.4±0.14 μM (r=0.98) and62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50values of these two drugs were221.9±0.22 μM (r=0.98) and195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at2:1molar ratio showed the best synergistic interaction.Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.

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

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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