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Canonical and new generation anticancer drugs also target energy metabolism

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Abstract

Significant efforts have been made for the development of new anticancer drugs (protein kinase or proteasome inhibitors, monoclonal humanized antibodies) with presumably low or negligible side effects and high specificity. However, an in-depth analysis of the side effects of several currently used canonical (platin-based drugs, taxanes, anthracyclines, etoposides, antimetabolites) and new generation anticancer drugs as the first line of clinical treatment reveals significant perturbation of glycolysis and oxidative phosphorylation. Canonical and new generation drug side effects include decreased (1) intracellular ATP levels, (2) glycolytic/mitochondrial enzyme/transporter activities and/or (3) mitochondrial electrical membrane potentials. Furthermore, the anti-proliferative effects of these drugs are markedly attenuated in tumor rho (0) cells, in which functional mitochondria are absent; in addition, several anticancer drugs directly interact with isolated mitochondria affecting their functions. Therefore, several anticancer drugs also target the energy metabolism, and hence, the documented inhibitory effect of anticancer drugs on cancer growth should also be linked to the blocking of ATP supply pathways. These often overlooked effects of canonical and new generation anticancer drugs emphasize the role of energy metabolism in maintaining cancer cells viable and its targeting as a complementary and successful strategy for cancer treatment.

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Abbreviations

ETC:

Electron transport chain

OxPhos:

Oxidative phosphorylation

2-OGDH:

2-Oxoglutarate dehydrogenase complex

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Acknowledgments

The present work was partially supported by CONACyT-México Grant Nos. 107183 to SRE, 180322 to AMH and 80534 and 123636 to RMS; and Instituto de Ciencia y Tecnología del Distrito Federal Grant No. PICS08.

Conflict of interest

The authors declare there is no conflict of interest.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto Nacional de Cardiología, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080, Mexico, Mexico

    Sara Rodríguez-Enríquez, Juan Carlos Gallardo-Pérez, Ileana Hernández-Reséndiz, Alvaro Marín-Hernández, Silvia C. Pacheco-Velázquez, Sayra Y. López-Ramírez & Rafael Moreno-Sánchez

  2. Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerología, San Fernando, Mexico

    Sara Rodríguez-Enríquez

  3. Centro de Ciencias de Saúde, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Franklin D. Rumjanek

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  1. Sara Rodríguez-Enríquez
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  2. Juan Carlos Gallardo-Pérez
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Correspondence to Sara Rodríguez-Enríquez or Rafael Moreno-Sánchez.

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Rodríguez-Enríquez, S., Gallardo-Pérez, J.C., Hernández-Reséndiz, I. et al. Canonical and new generation anticancer drugs also target energy metabolism. Arch Toxicol 88, 1327–1350 (2014). https://doi.org/10.1007/s00204-014-1246-2

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