Lactate Induces Cisplatin Resistance in S. cerevisiae through a Rad4p-Dependent Process
Joint Authors
Amaral, Leslie
Mendes, Filipa
Côrte-Real, Manuela
Chaves, Susana Rodrigues
Sousa, Maria João
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-24
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Cisplatin is a widely used antineoplastic agent that has DNA as the main target, though cellular resistance hampers its therapeutic efficacy.
An emerging hallmark of cancer cells is their altered metabolism, characterized by increased glycolysis even under aerobic conditions, with increased lactate production (known as the Warburg effect).
Although this altered metabolism often results in increased resistance to chemotherapy, it also provides an opportunity for targeted therapeutic intervention.
It has been suggested that cisplatin cytotoxicity can be affected by tumor metabolism, though with varying effects.
We therefore sought to better characterize how lactate affects cisplatin sensitivity in the simplified Saccharomyces cerevisiae model.
We show that lactate renders yeast cells resistant to cisplatin, independently of growth rate or respiration ability.
We further show that histone acetylation is not affected, but histone phosphorylation is decreased in lactate-containing media.
Finally, we show that Rad4p, essential for nucleotide excision repair, is required for the observed phenotype and thus likely underlies the mechanism responsible for lactate-mediated resistance to cisplatin.
Overall, understanding how lactate modulates cisplatin sensitivity will aid in the development of new strategies to overcome drug resistance.
American Psychological Association (APA)
Amaral, Leslie& Mendes, Filipa& Côrte-Real, Manuela& Sousa, Maria João& Chaves, Susana Rodrigues. 2020. Lactate Induces Cisplatin Resistance in S. cerevisiae through a Rad4p-Dependent Process. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-8.
https://search.emarefa.net/detail/BIM-1204681
Modern Language Association (MLA)
Amaral, Leslie…[et al.]. Lactate Induces Cisplatin Resistance in S. cerevisiae through a Rad4p-Dependent Process. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-8.
https://search.emarefa.net/detail/BIM-1204681
American Medical Association (AMA)
Amaral, Leslie& Mendes, Filipa& Côrte-Real, Manuela& Sousa, Maria João& Chaves, Susana Rodrigues. Lactate Induces Cisplatin Resistance in S. cerevisiae through a Rad4p-Dependent Process. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-8.
https://search.emarefa.net/detail/BIM-1204681
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204681