ArticleJournal of bioenergetics and biomembranes2013
Cancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin.
Article in Journal of bioenergetics and biomembranes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 75 citations in OpenAlex.
- Cancer-associated fibroblasts: enablers of tumor drug resistance.Journal of translational medicine · 2026Review
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- CCL2 and Lactate from Chemotherapeutics-Treated Fibroblasts Drive Malignant Traits by Metabolic Rewiring in Low-Migrating Breast Cancer Cell Lines.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Natural products reverse cancer multidrug resistance.Frontiers in pharmacology · 2024Review
- Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance.Pharmaceutics · 2023Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- Cancer-associated fibroblasts: The chief architect in the tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- Glycolytic Inhibitors Potentiated the Activity of Paclitaxel and Their Nanoencapsulation Increased Their Delivery in a Lung Cancer Model.Pharmaceutics · 2022Article
- Tumorous expression of NAC1 restrains antitumor immunity through the LDHA-mediated immune evasion.Journal for immunotherapy of cancer · 2022Article
- Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures.Cancer cell international · 2022Review
- Brain pH Measurement Using AACID CEST MRI Incorporating the 2 ppm Amine Resonance.Tomography (Ann Arbor, Mich.) · 2022Article
- Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing.Oncology letters · 2022Article
- Proton pump inhibitors and sensitization of cancer cells to radiation therapy.Frontiers in oncology · 2022Review
- The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2022Review
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer.Cells · 2021Article
- Nuclear Receptor-Mediated Metabolic Reprogramming and the Impact on HR+ Breast Cancer.Cancers · 2021Review
- Prediagnosis and postdiagnosis leisure time physical activity and survival following diagnosis with ovarian cancer.International journal of cancer · 2021Article
- Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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