Type

Journal Article

Authors

M Helena Vasconcelos
Juan M Falcon-Perez
Robert O'Connor
Raquel T Lima
Sebastiaan van Liempd
Diana Cabrera
Milica Pesic
Michael Henry
Paula Meleady
Justyna Mleczko
and 2 others

Subjects

Medicine & Nursing

Topics
cancer treatment cancer cell lines s adenosylmethionine oxidative phosphorylation multidrug resistance pentose phosphate pathway cancer cells p gp

Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles. (2016)

Abstract Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M Helena Vasconcelos, Juan M Falcon-Perez, Robert O'Connor, Raquel T Lima, Sebastiaan van Liempd, Diana Cabrera, Milica Pesic, Michael Henry, Paula Meleady, Justyna Mleczko and 2 others

Experts in our system

1
M Helena Vasconcelos
Dublin City University
 
2
Robert O'Connor
Dublin City University
Total Publications: 74
 
3
Raquel T Lima
Dublin City University
Total Publications: 3
 
4
Michael Henry
Dublin City University
Total Publications: 99
 
5
Paula Meleady
Dublin City University
Total Publications: 115