Metformin induced lactic acidosis impaired response of cancer cells towards paclitaxel and doxorubicin: Role of monocarboxylate transporter.
A549 Cells
Acidosis, Lactic
/ chemically induced
Animals
Antineoplastic Agents
/ pharmacology
Breast Neoplasms
/ complications
Diabetes Mellitus, Type 2
/ complications
Doxorubicin
/ pharmacology
Female
Humans
Hypoglycemic Agents
/ adverse effects
Lung Neoplasms
/ complications
MCF-7 Cells
Metformin
/ adverse effects
Mice, Inbred NOD
Mice, SCID
Neoplasms
/ complications
Paclitaxel
/ pharmacology
Chemotherapeutic outcome
Lactic acidosis
MCTs
Metabolic reprogramming
Metformin
Tumor-microenvironment
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
15
10
2019
revised:
06
11
2020
accepted:
09
11
2020
pubmed:
20
11
2020
medline:
1
7
2021
entrez:
19
11
2020
Statut:
ppublish
Résumé
Abnormal glucose metabolism in cancer cells causes generation and secretion of excess lactate, which results in acidification of the extracellular microenvironment. This altered metabolism aids not only in survival and proliferation but also in suppressing immune-mediated destruction of cancer cells. However, how it influences the response of cancer cells to chemotherapeutic drugs is not clearly understood. We employed appropriate in vitro approaches to explore the role of mono-carboxylate transporter 4 (MCT4) mediated altered intra and extracellular pH on the outcome of the therapeutic efficacy of chemotherapeutic drugs in breast and lung cancer models. We demonstrate by in vitro experiments that inhibition of complex I enhances glycolysis and increases expression as well as membrane translocation of MCT4. It causes a decrease in extracellular pH (pH
Identifiants
pubmed: 33212188
pii: S0925-4439(20)30359-8
doi: 10.1016/j.bbadis.2020.166011
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Hypoglycemic Agents
0
Doxorubicin
80168379AG
Metformin
9100L32L2N
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166011Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.