A combination of inhibitors of glycolysis, glutaminolysis and de novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells Corrigendum in /10.3892/ol.2020.11303

Schcolnik‑Cabrera,Alejandro; Dominguez‑Gómez,Guadalupe; Chávez‑Blanco,Alma; Ramírez‑Yautentzi,Marisol; Morales‑Bárcenas,Rocío; Díaz‑Chávez,José; Taja‑Chayeb,Lucía; Dueñas‑González,Alfonso

doi:10.3892/ol.2019.11008

December-2019 Volume 18 Issue 6

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December-2019 Volume 18 Issue 6

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Article

A combination of inhibitors of glycolysis, glutaminolysis and de novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

Corrigendum in: /10.3892/ol.2020.11303

Authors:
- Alejandro Schcolnik‑Cabrera
- Guadalupe Dominguez‑Gómez
- Alma Chávez‑Blanco
- Marisol Ramírez‑Yautentzi
- Rocío Morales‑Bárcenas
- José Díaz‑Chávez
- Lucía Taja‑Chayeb
- Alfonso Dueñas‑González
View Affiliations / Copyright

Affiliations: Basic Research Division, National Cancer Institute, Mexico City 14080, Mexico
Pages: 6909-6916
|
Published online on: October 18, 2019

https://doi.org/10.3892/ol.2019.11008
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Abstract

Lonidamine, 6‑Diazo‑5‑oxo‑L‑norleucine (DON) and orlistat are well known inhibitors of glycolysis, glutaminolysis and of de novo fatty acid synthesis, respectively. Although their antitumor effects have been explored in detail, the potential inhibition of the malignant metabolic phenotype and its influence on the expression of chemokines and growth factors involved in colon cancer, have not been previously reported to the best of our knowledge. In the present study, dose‑response curves with orlistat, lonidamine or DON were generated from cell viability assays conducted in SW480 colon cancer cells. In addition, the synergistic effect of these compounds was evaluated in SW480 human colon cancer cells. The determination of the doses used for maximum synergistic efficacy led to the exploration of the mRNA levels of the target genes hexokinase‑2 (HK2), glutaminase‑1 (GLS‑1) and fatty acid synthase (FASN) in human SW480 and murine CT26.WT colon cancer cells. The cell viability was evaluated following transfection with small interfering (si)RNA targeting these genes and was assessed with trypan blue. The expression levels of chemokines and growth factors were quantified in the supernatant of SW480 cells with LEGENDplex™. The combination of lonidamine, DON and orlistat resulted in a synergistic cytotoxic effect and induced the transcription of the corresponding gene targets but their corresponding proteins were actually downregulated. The downregulation of the expression levels of HK2, GLS‑1 and FASN following transfection of the cells with the corresponding siRNA sequences decreased their viability. The treatment significantly reduced the expression levels of 9 chemokines [interleukin‑9, C‑X‑C motif chemokine ligand (CXCL) 10, eotaxin, chemokine ligand (CCL) 9, CXCL5, CCL20, CXCL1, CXCL11 and CCCL4] and one growth factor (stem cell factor). These changes were associated with decreased phosphorylated‑nuclear factor κB‑p65. The data demonstrate that lonidamine, DON and orlistat in combination reduce the expression levels of chemokines and growth factors in colon cancer cells. Additional research is required to investigate the exact way by which both tumor and stromal cells regulate the expression levels of chemokines and growth factors.

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