scholarly journals Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway

2018 ◽  
Vol 46 (2) ◽  
pp. 492-504 ◽  
Author(s):  
Xiangyuan Chen ◽  
Qichao Wu ◽  
Pengfei Sun ◽  
Yanjun Zhao ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Hypoxia Inducible Factor ◽  
Xenograft Model ◽  
Erk Pathway ◽  
Protein Levels ◽  
Colorectal Cancer Cells

Background/Aims: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model. Methods: Glucose metabolism was assessed by measuring the extracellular acidification rate in HT29 and SW480 colorectal cancer cells. Quantitative real-time PCR and western blot analyses were used to detect mRNA and protein levels, respectively. Intracellular calcium was assessed by using a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was used to analyze glucose metabolism in the tumors of the xenograft model. Results: Propofol exposure induced a dose-dependent decrease of aerobic glycolysis in HT29 and SW480 colorectal cancer cells. MicroPET/CT indicated that propofol also inhibited 18F-FDG uptake in the xenograft model. In addition, hypoxia-inducible factor 1α (HIF1α) was also reduced by propofol dose-dependently. Propofol repressed the NMDAR-CAMKII-ERK pathway to inactivate HIF1α and therefore reduced glycolysis. Conclusion: Propofol inhibited aerobic glycolysis in colorectal cancer cells through the inactivation of the NMDAR-CAMKII-ERK pathway, which may facilitate a better understanding of the use of propofol in the clinical setting.

scholarly journals Effect of MED28 on Glucose Transporters and Glycolysis in Human Colorectal Cancer Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1248-1248
Author(s):  
Yu-Tsen Chang ◽  
Po-Chen Li ◽  
An-Chin Cheng ◽  
Ming-Fen Lee
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Glucose Transporters ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells ◽  
Hct116 Cells

Abstract Objectives MED28 exhibits several cellular roles, including a Mediator subunit for transcriptional activation as well as an interactor with merlin, NF2 tumor suppressor protein, and Grb2, a signaling adaptor. Our laboratory has previously reported that MED28 not only mediates cell growth but also appears to regulate glucose metabolism in human colorectal cancer cells. Therefore, the objective of the current study is to investigate the in vivo effect of MED28 on glucose metabolism and cell growth in colorectal cancer. Methods HCT116 colorectal cancer cells were transfected with MED28 siRNA or non-target siRNA for 72 h, and then undergone Western blotting or immunofluorescence analysis, by incubating with anti-c-Myc antibodies and DAPI for nuclear staining. We also established shMED28-transfected HCT116 cells and employed a NOD/SCID immunodeficient mouse xenograft model by subcutaneously implanting 1 × 107 stably transfected cells to the flanks of the animals to study the in vivo effect of MED28 expression on glucose metabolism. The animal study continued for 21 days, and the animal use protocol was approved by the Institutional Animal Care and Use Committee. The subcutaneous tumors were analyzed for the expression of MED28, glucose transporter 1 (GLUT1), and glycolysis-associated enzymes, including hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Results The expression of c-Myc was decreased upon MED28 knockdown in HCT116 cells. Our in vivo data indicated smaller xenograft volumes and lower expression levels of MED28, GLUT1, HK2, and LDHA in tumors carrying shMED28-transfected HCT116 cells than those of control counterparts. Conclusions MED28 upregulates glucose transporters and glycolysis-associated enzymes as well as cell growth in NOD/SCID subcutaneous xenografts, suggesting nutrient-gene interactions between glucose metabolism and MED28 in human colorectal cancer cells. Funding Sources This work was supported by the grants MOST106–2320-B-039–062-MY3 and CMU108-SR-31 to M-F Lee, and MOST108–2813-C-039–058-B to Y-T Chang.

scholarly journals B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2

Oncogene ◽  
2021 ◽  
Author(s):  
Xiaoyan Fan ◽  
Yitao Wang ◽  
Tinghui Jiang ◽  
Tao Liu ◽  
Yuelei Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Gene Expression Regulation ◽  
Critical Role ◽  
Feed Forward ◽  
Protein Levels ◽  
Colorectal Cancer Cells

AbstractB-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts. B-Myb overexpression accelerated cell proliferation, cell cycle progression and cell motility in colorectal cancer cells, and promoted tumor growth in orthotopic nude mouse models in vivo. In contrast, B-Myb depletion inhibited these malignant phenotypes. Mechanistic investigations revealed that E2F2 was a novel transcriptional target of B-Myb and is essential to B-Myb-induced malignant phenotypes. Notably, B-Myb and E2F2 exhibited positive expression correlation, and interacted with each other in colorectal cancer cells. In addition to their autoregulatory mechanisms, B-Myb and E2F2 can also directly transactivate each other, thus constituting consolidated reciprocal feed-forward transactivation loops. Moreover, both B-Myb and E2F2 are required for the activation of ERK and AKT signaling pathways in colorectal cancer cells. Taken together, our data clarified a critical role for B-Myb in colorectal cancer and unraveled an exquisite mutual collaboration and reciprocal cross regulation between B-Myb and E2F2 that contribute to the malignant progression of human colorectal cancer.

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

scholarly journals Circ-BANP Contributes to Cell Carcinogenesis and Aerobic Glycolysis by Regulating MAPK1 Through miR-874-3p in Colorectal Cancer

2021 ◽  
Author(s):  
Yunxin Zhang ◽  
Kexin Shen ◽  
Hanyi Zha ◽  
Wentao Zhang ◽  
Haishan Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Xenograft Model ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Luciferase Reporter

Abstract BackgroundCircular RNA-BTG3 associated nuclear protein (circ-BANP) was identifified to involve in cell proliferation of colorectal cancer (CRC). The aerobic glycolysis is a key metabolism mediating cancer progression. However, the role of circ-BANP on aerobic glycolysis in CRC remains unknown. MethodsThe expression of circ-BANP, microRNA (miR)-874-3p, and mitogen-activated protein kinase 1 (MAPK1) mNRA was detected using quantitative real-time polymerase chain reaction. Cell viability and invasion were measured by cell counting kit-8 assay or transwell assay. Glucose consumption and lactate production were assessed by a glucose and lactate assay kit. XF Extracellular Flux Analyzer was used to determine extracellular acidifification rate (ECAR). Western blot was used to analyze the levels of hexokinase-2 (HK2), pyruvate kinase M2 (PKM2), MAPK1, proliferating cell nuclear antigen (PCNA), Cyclin D1, N-cadherin, E-cadherin, hypoxia inducible factor-1α (HIF-1α), glucose transport protein 1(GLUT1), and c-Myc. The interaction between miR-874-3p and circ-BANP or MAPK1 was confifirmed by dual luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model. ResultsCirc-BANP was up-regulated in CRC tissues and cell lines. Circ-BANP knockdown suppressed CRC cell proliferation, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Circ-BANP was a sponge of miR-874-3p and performed anti-tumor effffects by binding to miR-874-3p in CRC cells. Subsequently, we confifirmed MAPK1 was a target of miR-874-3p and circ-BANP indirectly regulated MAPK1 expression by sponging miR-874-3p. After that, we found MAPK1 overexpression partially reversed circ-BANP deletion-mediated inhibition on cell carcinogenesis and aerobic glycolysis in CRC. ConclusionCirc-BANP accelerated cell carcinogenesis and aerobic glycolysis by regulating MAPK1 through miR- 874-3p in CRC, suggesting a promising therapeutic strategy for CRC treatment.

In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

2013 ◽  
Vol 86 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Joseph W. Shelton ◽  
Timothy V. Waxweiler ◽  
Jerome Landry ◽  
Huiying Gao ◽  
Yanbo Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Colorectal Cancer Cells

Transfection of PDCD5 sensitizes colorectal cancer cells to cisplatin-induced apoptosis in vitro and in vivo

2010 ◽  
Vol 649 (1-3) ◽  
pp. 120-126 ◽  
Author(s):  
Anning Yin ◽  
Yingan Jiang ◽  
Xianfeng Zhang ◽  
Juan Zhao ◽  
Hesheng Luo
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

scholarly journals Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo

2017 ◽  
Vol 13 (6) ◽  
pp. 4762-4768 ◽  
Author(s):  
Ying Wang ◽  
Shoujun Yuan ◽  
Linna Li ◽  
Dexuan Yang ◽  
Chengwang Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Colorectal Cancer Cells
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