Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/26983

TitleCancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin
Author(s)Valente, Diana Tavares
Baltazar, Fátima
Moreira, Roxana
Queirós, Odília
Keywords“Warburg effect”
Multidrug resistance (MDR)
Extracellular pH
Bioenergetic modulators
Issue date2013
PublisherSpringer
JournalJournal of bioenergetics and biomembranes
Abstract(s)The multidrug resistance (MDR) phenotype, frequently observed during cancer treatment, is often associated with drug efflux pump activity. However, many other factors are also known to be involved. Cancer cells often rely on aerobic glycolysis for energy production; this is known as the "Warburg effect" and is used as a survival mechanism. Associated to this event, a reverse pH gradient across the cell membrane occurs, leading to cytosol alkalinization and extracellular acidification. In the present study, we investigated the role of different mechanisms involved in MDR, such as altered tumor microenvironment and energetic metabolism. The breast cancer cell line MCF-7, used as model, was exposed to two widely used antitumor drugs, paclitaxel (antimitotic agent) and doxorubicin (alkylating agent). Cancer pH regulation was shown to be crucial for malignant characteristics such as cell migration and drug resistance. Our results showed that a lower extracellular pH induced a higher migratory capacity and higher resistance to the studied chemotherapeutical compounds in MCF-7 cells. Besides the influence of the extracellular pH, the role of the tumor metabolism in the MDR phenotype was also investigated. Pre-treatment with different bioenergetic modulators led to cell ATP depletion and altered lactic acid production and glucose consumption, resulting in increased sensitivity to paclitaxel and doxorubicin. Overall, this study supports the potential use of compounds targeting cell metabolism and tumor microenvironment factors such as pH, as co-adjuvants in conventional chemotherapy.
TypeArticle
URIhttp://hdl.handle.net/1822/26983
DOI10.1007/s10863-013-9519-7
ISSN0145-479X
1573-6881
Publisher versionhttp://www.springer.com/chemistry/organic+chemistry/journal/10863
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
tavares-valente d_j bioenerg biomembr 2013 need posp.pdf
  Restricted access
610,02 kBAdobe PDFView/Open    Request a copy!

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID