Next Article in Journal
Oral Intake of Collagen Peptide Attenuates Ultraviolet B Irradiation-Induced Skin Dehydration In Vivo by Regulating Hyaluronic Acid Synthesis
Next Article in Special Issue
From Friend to Enemy: Dissecting the Functional Alteration of Immunoregulatory Components during Pancreatic Tumorigenesis
Previous Article in Journal
Cellular and Molecular Events in the Airway Epithelium Defining the Interaction Between House Dust Mite Group 1 Allergens and Innate Defences
Previous Article in Special Issue
The Novel Autophagy Inhibitor Alpha-Hederin Promoted Paclitaxel Cytotoxicity by Increasing Reactive Oxygen Species Accumulation in Non-Small Cell Lung Cancer Cells
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(11), 3550; https://doi.org/10.3390/ijms19113550

Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells

Department of Oncology, University of Torino, Via Santena 5/bis, 10126 Torino, Italy
*
Authors to whom correspondence should be addressed.
Received: 30 August 2018 / Revised: 6 November 2018 / Accepted: 8 November 2018 / Published: 10 November 2018
Full-Text   |   PDF [7602 KB, uploaded 10 November 2018]   |  

Abstract

Emerging evidence supports the idea that a dysfunction in cell metabolism could sustain a resistant phenotype in cancer cells. As the success of chemotherapeutic agents is often questioned by the occurrence of multidrug resistance (MDR), a multiple cross-resistance towards different anti-cancer drugs represent a major obstacle to cancer treatment. The present study has clarified the involvement of the carbon metabolites in a more aggressive tumor colon adenocarcinoma phenotype and in a chemoresistant mesothelioma, and the role of pyruvate treatment in the reversion of the potentially related resistance. For the first time, we have shown that human colon adenocarcinoma cells (HT29) and its chemoresistant counterpart (HT29-dx) displayed different carbon metabolism: HT29-dx cells had a higher glucose consumption compared to HT29 cells, whereas human malignant mesothelioma (HMM) cells showed a lower glucose consumption compared to HT29 cells, accompanied by a lower pyruvate production and, consequently, a higher production of lactate. When treated with pyruvate, both HT29-dx and HMM cells exhibited a re-established accumulation of doxorubicin and a lower survival ability, a decreased activity of multidrug resistance protein 1 (MRP1) and a restored mitochondrial respiratory chain function, improving the effectiveness of the chemotherapeutic agents in these resistant cancer cells. View Full-Text
Keywords: chemoresistance; pyruvate; carbon metabolism; mitochondria respiratory chain; human colon adenocarcinoma cells; human pleural mesothelioma cells chemoresistance; pyruvate; carbon metabolism; mitochondria respiratory chain; human colon adenocarcinoma cells; human pleural mesothelioma cells
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Mungo, E.; Bergandi, L.; Salaroglio, I.C.; Doublier, S. Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells. Int. J. Mol. Sci. 2018, 19, 3550.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top