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Updated: Apr 30, 2026
Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
Canonical and new generation anticancer drugs also target energy metabolism
Sara Rodríguez-Enríquez1, Juan Carlos Gallardo-Pérez, Ileana Hernández-Reséndiz
1Departamento de Bioquímica, Instituto Nacional de Cardiología, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080, Mexico, Mexico, saren960104@hotmail.com.
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.
Insights
Anticancer drugs, both old and new, disrupt cancer cell energy metabolism, significantly impacting ATP production and mitochondrial function. Targeting these metabolic pathways offers a promising complementary cancer treatment strategy.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Modern anticancer drugs aim for high specificity and low side effects.
- Canonical and novel cancer therapies are increasingly scrutinized for their impact on cellular energy production.
Purpose of the Study:
- To investigate the effects of canonical and new generation anticancer drugs on cellular energy metabolism.
- To determine if anticancer drug efficacy is linked to the inhibition of ATP synthesis pathways.
Main Methods:
- Analysis of side effects of various anticancer drugs on glycolysis and oxidative phosphorylation.
- Assessment of intracellular ATP levels, enzyme/transporter activities, and mitochondrial membrane potentials.
- Evaluation of drug effects on tumor rho (0) cells lacking mitochondria.
Main Results:
- Anticancer drugs significantly perturb glycolysis and oxidative phosphorylation.
- Observed decreases in intracellular ATP, enzyme activities, and mitochondrial membrane potentials.
- Anti-proliferative effects were reduced in cells lacking functional mitochondria, indicating a role for energy metabolism.
Conclusions:
- Anticancer drugs target cellular energy metabolism, including ATP supply pathways.
- The efficacy of anticancer drugs is partly due to the blockade of energy metabolism.
- Targeting cancer cell energy metabolism represents a viable complementary therapeutic strategy.
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