The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

  • Authors:
    • Yuta Sugiyama
    • Yuichiro Hagiya
    • Motowo Nakajima
    • Masahiro Ishizuka
    • Tohru Tanaka
    • Shun-Ichiro Ogura
  • View Affiliations

  • Published online on: December 23, 2013     https://doi.org/10.3892/or.2013.2945
  • Pages: 1282-1286
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Abstract

Our previous study demonstrated that 5-aminolevulinic acid (ALA) administered to mice stimulates oxidative phosphorylation by upregulation of the mitochondrial respiratory chain complex IV enzyme cytochrome c oxidase (COX). The present study investigated whether ALA disrupts the Warburg effect, which represents a shift in ATP generation from oxidative phosphorylation to glycolysis, protecting tumor cells against oxidative stress-mediated apoptosis. The human lung carcinoma cell line A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption. Furthermore, ALA suppressed glycolysis-mediated acidosis. This normalization of the ATP metabolic pathways significantly increased the generation of superoxide anion radical (O2•-) and the functional expression of active caspase-3, leading to caspase-dependent apoptosis. These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death. Use of this endogenous compound might constitute a novel approach to cancer therapy.
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2014-March
Volume 31 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sugiyama Y, Hagiya Y, Nakajima M, Ishizuka M, Tanaka T and Ogura S: The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis. Oncol Rep 31: 1282-1286, 2014.
APA
Sugiyama, Y., Hagiya, Y., Nakajima, M., Ishizuka, M., Tanaka, T., & Ogura, S. (2014). The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis. Oncology Reports, 31, 1282-1286. https://doi.org/10.3892/or.2013.2945
MLA
Sugiyama, Y., Hagiya, Y., Nakajima, M., Ishizuka, M., Tanaka, T., Ogura, S."The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis". Oncology Reports 31.3 (2014): 1282-1286.
Chicago
Sugiyama, Y., Hagiya, Y., Nakajima, M., Ishizuka, M., Tanaka, T., Ogura, S."The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis". Oncology Reports 31, no. 3 (2014): 1282-1286. https://doi.org/10.3892/or.2013.2945