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Cancers
Special Issues
The Role of Lactate Isomers in Cancer
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The Role of Lactate Isomers in Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 6230

Special Issue Editors

Dr. Lidia de Bari

E-Mail Website
Guest Editor
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), Italian National Research Council (CNR), Bari, Italy
Interests: cell metabolism; cancer cells; cancer biomarkers; cancer metabolism; mitochondria; bioenergetics; biochemistry; L-lactate; D-lactate; glyoxalases; neurodegenerative diseases
Dr. Miklós Péter Kalapos

E-Mail Website
Co-Guest Editor
Theoretical Biology Research Group, Budapest, Hungary
Interests: methylglyoxal; glyoxalases; cell metabolism; glycolysis; chemistry; biochemistry; S-D-lactoylglutathione; D-lactate; S-glutathionylation, evolution.

Special Issue Information

Dear colleagues,

L- and D-lactate both derive from the triose phosphate intermediates of glycolysis. Since the rate of glycolysis increases in tumors, both L- and D-lactate formation could be considered a hallmark of increased glucose consumption in cancer. Even if far less is known about D-lactate than L-isomer, especially in cancer, the importance of both L- and D-lactate formation, transport, and metabolic fate clearly emerges from earlier and recent discoveries.

This Special Issue focuses on the study of lactate isomers, from their production to their transport and oxidation, both in normal and cancer cells, stressing the role of these compounds in cell metabolism, signaling, as well as in cell interactions within the tumor. Studies exploring the involvement of mitochondria in these processes are also welcome.

We firmly believe that the present Special Issue, by bringing together all the achievements on lactate biochemistry, will represent an important overview on this complex topic and highlight the missing tiles from a mosaic that promises to indicate novel therapeutic perspectives for the cure of cancer patients.

For this Special Issue, original research articles and reviews are equally welcome.

We look forward to receiving your contributions.

Dr. Lidia de Bari
Dr. Miklós Péter Kalapos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • L-lactate
  • D-lactate
  • glycolysis
  • mitochondria
  • glyoxalases
  • methylglyoxal
  • lactate transport
  • signaling
  • triose phosphates

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Published Papers (2 papers)

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15 pages, 7120 KiB  
Article
Discovery of Mitochondrial Complex I Inhibitors as Anticancer and Radiosensitizer Drugs Based on Compensatory Stimulation of Lactate Release
by Junjie Lan, Octavia Cadassou, Cyril Corbet, Olivier Riant and Olivier Feron
Cancers 2022, 14(21), 5454; https://doi.org/10.3390/cancers14215454 - 6 Nov 2022
Cited by 6 | Viewed by 2174
Abstract
Cancer cells may stimulate glycolytic flux when O2 becomes insufficient. Increase in L-lactate release therefore appears as an escape mechanism to drugs targeting mitochondrial respiration but also represents a response that may be exploited to screen for compounds blocking either mitochondrial carriers [...] Read more.
Cancer cells may stimulate glycolytic flux when O2 becomes insufficient. Increase in L-lactate release therefore appears as an escape mechanism to drugs targeting mitochondrial respiration but also represents a response that may be exploited to screen for compounds blocking either mitochondrial carriers of oxidizable substrates or the electron transport chain. Here, we developed a screening procedure based on the capacity of cancer cells to release L-lactate to gain insights on the development of mitochondrial complex I inhibitors. For this purpose, we synthesized derivatives of carboxyamidotriazole, a compound previously described as a potential OXPHOS inhibitor. Two series of derivatives were generated by cycloaddition between benzylazide and either cyanoacetamides or alkynes. A primary assay measuring L-lactate release as a compensatory mechanism upon OXPHOS inhibition led us to identify 15 hits among 28 derivatives. A secondary assay measuring O2 consumption in permeabilized cancer cells confirmed that 12 compounds among the hits exhibited reversible complex I inhibitory activity. Anticancer effects of a short list of 5 compounds identified to induce more L-lactate release than reference compound were then evaluated on cancer cells and tumor-mimicking 3D spheroids. Human and mouse cancer cell monolayers exhibiting high level of respiration in basal conditions were up to 3-fold more sensitive than less oxidative cancer cells. 3D tumor spheroids further revealed potency differences between selected compounds in terms of cytotoxicity but also radiosensitizing activity resulting from local reoxygenation. In conclusion, this study documents the feasibility to efficiently screen in 96-well plate format for mitochondrial complex I inhibitors based on the capacity of drug candidates to induce L-lactate release. Full article
(This article belongs to the Special Issue The Role of Lactate Isomers in Cancer)
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Review

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28 pages, 1095 KiB  
Review
Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers
by Ming Cai, Jian Wan, Keren Cai, Haihan Song, Yujiao Wang, Wanju Sun and Jingyun Hu
Cancers 2023, 15(1), 87; https://doi.org/10.3390/cancers15010087 - 23 Dec 2022
Cited by 13 | Viewed by 3301
Abstract
Lactate mediates multiple cell-intrinsic effects in cancer metabolism in terms of development, maintenance, and metastasis and is often correlated with poor prognosis. Its functions are undertaken as an energy source for neighboring carcinoma cells and serve as a lactormone for oncogenic signaling pathways. [...] Read more.
Lactate mediates multiple cell-intrinsic effects in cancer metabolism in terms of development, maintenance, and metastasis and is often correlated with poor prognosis. Its functions are undertaken as an energy source for neighboring carcinoma cells and serve as a lactormone for oncogenic signaling pathways. Indeed, two isomers of lactate are produced in the Warburg effect: L-lactate and D-lactate. L-lactate is the main end-production of glycolytic fermentation which catalyzes glucose, and tiny D-lactate is fabricated through the glyoxalase system. Their production inevitably affects cancer development and therapy. Here, we systematically review the mechanisms of lactate isomers production, and highlight emerging evidence of the carcinogenic biological effects of lactate and its isomers in cancer. Accordingly, therapy that targets lactate and its metabolism is a promising approach for anticancer treatment. Full article
(This article belongs to the Special Issue The Role of Lactate Isomers in Cancer)
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