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A short review on creatine–creatine kinase system in relation to cancer and some experimental results on creatine as adjuvant in cancer therapy

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Abstract

The creatine/creatine kinase (CK) system plays a key role in cellular energy buffering and transport. In vertebrates, CK has four isoforms expressed in a tissue-specific manner. In the process of creatine biosynthesis several other important metabolites are formed. The anticancer effect of creatine had been reported in the past, and recent literature has reported low creatine content in several types of malignant cells. Furthermore, creatine can protect cardiac mitochondria from the deleterious effects of some anticancer compounds. Previous work from our laboratory showed progressive decrease of phosphocreatine, creatine and CK upon transformation of skeletal muscle into sarcoma. It was convincingly demonstrated that prominent expression of creatine-synthesizing enzymes l-arginine: glycine amidinotransferase and N-guanidinoacetate methyltransferase occurs in sarcoma, Ehrlich ascites carcinoma and sarcoma 180 cells; whereas, both these enzymes are virtually undetectable in skeletal muscle. Creatine transporter also remained unaltered in malignant cells. The anticancer effect of methylglyoxal had been known for a long time. The present work shows that this anticancer effect of methylglyoxal is significantly augmented in presence of creatine. On creatine supplementation the effect of methylglyoxal plus ascorbic acid was further augmented and there was no visible sign of tumor. Moreover, creatine and CK, which were very low in sarcoma tissue, were significantly elevated with the concomitant regression of tumor.

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Abbreviations

AGAT:

l-Arginine: glycine amidinotransferase

CK:

Creatine kinase

EAC:

Ehrlich ascites carcinoma

GAMT:

N-guanidinoacetate methyltransferase

MCK:

Muscle-specific cytosolic CK

BCK:

Brain-specific cytosolic CK

MitCK:

Mitochondrial CK

sMitCK:

Sarcomeric MitCK

uMitCK:

Ubiquitous MitCK

MPT:

Mitochondrial permeability transition

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Acknowledgments

This work was supported by grants from Council of Scientific and Industrial Research, and Department of Science and Technology, India.

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Authors and Affiliations

  1. Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata, 700 032, India

    Subrata Patra, Alok Ghosh, Soumya Sinha Roy, Soumen Bera, Manju Das & Dipa Talukdar

  2. 13 Regent Estate, Kolkata, 700 092, India

    Subhankar Ray

  3. Institute of Cell Biology, ETH Zurich, 8093, Zurich, Switzerland

    Theo Wallimann

  4. Division of Molecular Medicine, Bose Institute, Kolkata, 700 054, India

    Manju Ray

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  1. Subrata Patra
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  2. Alok Ghosh
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Correspondence to Manju Ray.

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S. Patra and A. Ghosh have contributed equally to this work.

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Patra, S., Ghosh, A., Roy, S.S. et al. A short review on creatine–creatine kinase system in relation to cancer and some experimental results on creatine as adjuvant in cancer therapy. Amino Acids 42, 2319–2330 (2012). https://doi.org/10.1007/s00726-011-0974-3

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