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Article

Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer

  • Authors:
    • Diana Cervantes‑Madrid
    • Guadalupe Dominguez‑Gomez
    • Aurora Gonzalez‑Fierro
    • Enrique Perez‑Cardenas
    • Lucia Taja‑Chayeb
    • Catalina Trejo-Becerril
    • Alfonso Duenas‑Gonzalez
  • View Affiliations / Copyright

    Affiliations: Division of Basic Research, National Cancer Institute, Mexico City 14080, Mexico, Unit of Biomedical Research on Cancer, Institute of Biomedical Investigations, National Autonomous University of Mexico/National Cancer Institute, Mexico City 14080, Mexico
  • Pages: 1905-1910
    |
    Published online on: January 18, 2017
       https://doi.org/10.3892/ol.2017.5615
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Abstract

The aim of the present study was to investigate in vivo the feasibility and efficacy of the combination of lonidamine (LND), 6‑diazo‑5‑oxo‑L‑norleucine (DON) and orlistat to simultaneously target glycolysis, glutaminolysis and de novo synthesis of fatty acids, respectively. The doses of LND and DON used in humans were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at different doses were administered by intraperitoneal injection to BALB/c mice in a 21‑day cycle (schedule 1: LND, 0.5 mg/day; DON, 0.25 mg/day 1, 5 and 9; orlistat, 240 mg/kg/day; schedule 2: LND, 0.1 mg/day; DON, 0.5 mg/day 1, 5 and 9; orlistat, 240 mg/kg/day; schedule 3: LND, 0.5 mg/day; DON, 0.08 mg/day 1, 5 and 9; orlistat, 360 mg/kg/day) to assess tolerability. To determine the antitumor efficacy, a syngeneic tumor model in BALB/c mice was created using colon cancer CT26.WT cells, and a xenogeneic tumor model was created in nude mice using the human colon cancer SW480 cell line. Mice were treated with schedule 1. Animals were weighed, clinically inspected during the experiment and the tumor volume was measured at day 21. The 3 schedules assessed in the tolerability experiments were well tolerated, as mice maintained their weight and no evident clinical signs of toxicity were observed. Combination treatment with schedule 1 significantly decreased tumor growth in each mouse model. No evident signs of toxicity were observed and mice maintained their weight during treatment. The triple metabolic blockade of the malignant phenotype appears feasible and promising for cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Cervantes‑Madrid D, Dominguez‑Gomez G, Gonzalez‑Fierro A, Perez‑Cardenas E, Taja‑Chayeb L, Trejo-Becerril C and Duenas‑Gonzalez A: Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer. Oncol Lett 13: 1905-1910, 2017.
APA
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., & Duenas‑Gonzalez, A. (2017). Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer. Oncology Letters, 13, 1905-1910. https://doi.org/10.3892/ol.2017.5615
MLA
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., Duenas‑Gonzalez, A."Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer". Oncology Letters 13.3 (2017): 1905-1910.
Chicago
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., Duenas‑Gonzalez, A."Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer". Oncology Letters 13, no. 3 (2017): 1905-1910. https://doi.org/10.3892/ol.2017.5615
Copy and paste a formatted citation
x
Spandidos Publications style
Cervantes‑Madrid D, Dominguez‑Gomez G, Gonzalez‑Fierro A, Perez‑Cardenas E, Taja‑Chayeb L, Trejo-Becerril C and Duenas‑Gonzalez A: Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer. Oncol Lett 13: 1905-1910, 2017.
APA
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., & Duenas‑Gonzalez, A. (2017). Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer. Oncology Letters, 13, 1905-1910. https://doi.org/10.3892/ol.2017.5615
MLA
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., Duenas‑Gonzalez, A."Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer". Oncology Letters 13.3 (2017): 1905-1910.
Chicago
Cervantes‑Madrid, D., Dominguez‑Gomez, G., Gonzalez‑Fierro, A., Perez‑Cardenas, E., Taja‑Chayeb, L., Trejo-Becerril, C., Duenas‑Gonzalez, A."Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6‑diazo‑5‑oxo‑L‑norleucine and orlistat in colon cancer". Oncology Letters 13, no. 3 (2017): 1905-1910. https://doi.org/10.3892/ol.2017.5615
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