Nrf2‐Activating Phytochemicals, Sulforaphane and Licochalcone A, Stimulate Cell Growth‐Regulating Kinases in HCT116 Human Colorectal Cancer Cells

Polyamines are essential growth factors that have a positive role in cancer cell growth. Their metabolic pathway and the diverse enzymes involved have been studied in depth in multiple organisms and cells. Polyamine transport also contributes to the intracellular polyamine content but this is less well-studied in mammalian cells. As the polyamine transporters could provide a means of selective drug delivery to cancer cells, a greater understanding of polyamine transport and its regulation is needed. In this study, transport of polyamines and polyamine content was measured and the effect of modulating each was determined in human colorectal cancer cells. The results provide evidence that upregulation of polyamine transport depends on polyamine depletion and on the rate of cell growth. Polyamine transport occurred in all colorectal cancer cell lines tested but to varying extents. The cell lines with the lowest basal uptake showed the greatest increase in response to polyamine depletion. Kinetic parameters for putrescine and spermidine suggest the existence of two separate transporters. Transport was shown to be a saturable but non-polarised process that can be regulated both positively and negatively. Using the polyamine transporter to deliver anticancer drugs more selectively is now a reality, and the ability to manipulate the polyamine transport process increases the possibility of using these transporters therapeutically.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_006 ◽

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.

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Calcitriol Suppresses Warburg Effect and Cell Growth in Human Colorectal Cancer Cells

Life ◽

10.3390/life11090963 ◽

2021 ◽

Vol 11 (9) ◽

pp. 963

Author(s):

Chun-Yin Huang ◽

Yu-Ting Weng ◽

Po-Chen Li ◽

Nien-Tsu Hsieh ◽

Chun-I Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Warburg Effect ◽

Active Form ◽

Biologically Active ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D3), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the “Warburg effect” to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.

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