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Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin

Investigational New Drugs volume 31, pages 256–264 (2013)Cite this article

Summary

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

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Acknowledgments

We acknowledge the help of Edward Sanders. The studies were performed by Nosco Pharmaceuticals (France). This work was funded by Biorébus.

Conflict of interest

METABLOC is a trade mark of Biorébus.

AG is an employee of Biorébus. The other authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Ecole Polytechnique, Laboratoire d’Informatique, Palaiseau, France

    Laurent Schwartz & Jean-Marc Steyaert

  2. AP-HP, Hôpital Raymond Poincaré, Service d’Oncologie, Garches, France

    Laurent Schwartz

  3. Biorébus, Paris, France

    Adeline Guais & Maurice Israël

  4. Formindep, Roubaix, France

    Bernard Junod

  5. METABLOC Cancer Center, Centro Medico Kines, Castano Primo, Milan, Italy

    Elisabetta Crespi & Gianfranco Baronzio

  6. Nosco Pharmaceuticals, Paris, France

    Mohammad Abolhassani

  7. Ecole Polytechnique Laboratoire LIX, 91128, Palaiseau, France

    Laurent Schwartz

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  1. Laurent Schwartz
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  2. Adeline Guais
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  3. Maurice Israël
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Correspondence to Laurent Schwartz.

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Supplementary Fig. 1

Summary statistics used when comparing outcomes between mice treated and not treated. Two statistics were used for analyzing in vivo tumor growth and response to treatment. Left - T/C%, the ratio of change over time in median tumor volume in percent for groups treated with capsaicin and for control groups; Right - Rp, the ratio dividing successes by failures of treatment with capsaicin across all possible pairs of mice, one coming from a treated group and the other from a control group. A ratio Rp = St/Ft lower than 1.0 would mean that the volume of the tumor is likely to increase more often in the treated group than in the control group (less successes than failures); a ratio larger than 1.0 would mean that the volume of the tumor is likely to increase less often in the treated group than in the control group (more successes than failures). The TVI (tumor volume increase) is obtained by subtracting the reference volume measured on the first day of treatment. (PDF 12 kb)

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Schwartz, L., Guais, A., Israël, M. et al. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin. Invest New Drugs 31, 256–264 (2013). https://doi.org/10.1007/s10637-012-9849-z

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  • DOI: https://doi.org/10.1007/s10637-012-9849-z

Keywords

  • Cancer
  • Metabolism
  • Metabloc
  • Capsaicin
  • Warburg