Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
01
04
2021
accepted:
06
09
2021
entrez:
2
11
2021
pubmed:
3
11
2021
medline:
21
1
2022
Statut:
epublish
Résumé
Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence and currently evaluated in cancer clinical trials. The combined treatment with metformin and 2-deoxy-D-glucose (2DG) in vitro induces detachment of viable MDA-MB-231 breast cancer cells that retain their proliferation capacity. This might be important for cell detachment from primary tumors, but the metabolic changes involved are unknown. We performed LC/MS metabolic profiling on separated attached and detached MDA-MB-231 cells treated with metformin and/or 2DG. High 2DG and metformin plus 2DG altered the metabolic profile similarly to metformin, inferring that metabolic changes are necessary but not sufficient while the specific effects of 2DG are crucial for detachment. Detached cells had higher NADPH levels and lower fatty acids and glutamine levels compared to attached cells, supporting the role of AMPK activation and reductive carboxylation in supporting anchorage-independent survival. Surprisingly, the metabolic profile of detached cells was closer to untreated control cells than attached treated cells, suggesting detachment might help cells adapt to energy stress. Metformin treated cells had higher fatty and amino acid levels with lower purine nucleotide levels, which is relevant for understanding the anticancer mechanisms of metformin.
Identifiants
pubmed: 34725457
doi: 10.1038/s41598-021-98642-0
pii: 10.1038/s41598-021-98642-0
pmc: PMC8560930
doi:
Substances chimiques
Hypoglycemic Agents
0
Metformin
9100L32L2N
Deoxyglucose
9G2MP84A8W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21354Subventions
Organisme : Slovenian Research Agency
ID : P1-0055
Organisme : Slovenian Research Agency
ID : P3-0067
Organisme : Slovenian Research Agency
ID : P1-0055
Organisme : Slovenian Research Agency
ID : P3-0067
Organisme : Slovenian Research Agency
ID : P1-0055
Organisme : Ministry of Education, Science and Sport of the Republic of Slovenia
ID : C3330-19-952026
Organisme : Ministry of Education, Science and Sport of the Republic of Slovenia
ID : C3330-19-952026
Informations de copyright
© 2021. The Author(s).
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