Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming Article Swipe
Ioannis S. Pateras
,
Chloe Williams
,
Despoina D. Gianniou
,
Aggelos T. Margetis
,
Margaritis Avgeris
,
Pantelis Rousakis
,
Aigli‐Ioanna Legaki
,
Peter Mirtschink
,
Wei Zhang
,
Konstantina Panoutsopoulou
,
Anastasios Delis
,
Stamatis N. Pagakis
,
Wei Tang
,
Stefan Ambs
,
Ulrika Warpman Berglund
,
Thomas Helleday
,
Anastasia Varvarigou
,
Antonios Chatzigeorgiou
,
Anders Nordström
,
Ourania Tsitsilonis
,
Ioannis P. Trougakos
,
Jonathan D. Gilthorpe
,
Teresa Frisan
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s12967-023-03935-9
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s12967-023-03935-9
Background Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized. Methods The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H 2 DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model. Results We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model. Conclusions Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s12967-023-03935-9
- https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-03935-9
- OA Status
- gold
- Cited By
- 27
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4323042386
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4323042386Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s12967-023-03935-9Digital Object Identifier
- Title
-
Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogrammingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-03-03Full publication date if available
- Authors
-
Ioannis S. Pateras, Chloe Williams, Despoina D. Gianniou, Aggelos T. Margetis, Margaritis Avgeris, Pantelis Rousakis, Aigli‐Ioanna Legaki, Peter Mirtschink, Wei Zhang, Konstantina Panoutsopoulou, Anastasios Delis, Stamatis N. Pagakis, Wei Tang, Stefan Ambs, Ulrika Warpman Berglund, Thomas Helleday, Anastasia Varvarigou, Antonios Chatzigeorgiou, Anders Nordström, Ourania Tsitsilonis, Ioannis P. Trougakos, Jonathan D. Gilthorpe, Teresa FrisanList of authors in order
- Landing page
-
https://doi.org/10.1186/s12967-023-03935-9Publisher landing page
- PDF URL
-
https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-03935-9Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-03935-9Direct OA link when available
- Concepts
-
Triple-negative breast cancer, Reprogramming, Starvation, Breast cancer, Chemotherapy, Cancer research, Cancer, Medicine, Term (time), Oncology, Bioinformatics, Internal medicine, Biology, Pharmacology, Biochemistry, Gene, Quantum mechanics, PhysicsTop concepts (fields/topics) attached by OpenAlex
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27Total citation count in OpenAlex
- Citations by year (recent)
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2025: 7, 2024: 16, 2023: 4Per-year citation counts (last 5 years)
- References (count)
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61Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.combined | 74, 188, 261 |
| abstract_inverted_index.compared | 225 |
| abstract_inverted_index.effects. | 41 |
| abstract_inverted_index.efficacy | 55, 259 |
| abstract_inverted_index.enhanced | 192 |
| abstract_inverted_index.enhances | 176 |
| abstract_inverted_index.examined | 149 |
| abstract_inverted_index.fasting, | 48 |
| abstract_inverted_index.findings | 154, 280 |
| abstract_inverted_index.improves | 53 |
| abstract_inverted_index.insights | 170 |
| abstract_inverted_index.negative | 11 |
| abstract_inverted_index.periodic | 262 |
| abstract_inverted_index.profile, | 243 |
| abstract_inverted_index.reactive | 197 |
| abstract_inverted_index.regimes. | 25 |
| abstract_inverted_index.toxicity | 17 |
| abstract_inverted_index.validate | 255 |
| abstract_inverted_index.(Seahorse | 99 |
| abstract_inverted_index.analysis, | 100 |
| abstract_inverted_index.decreased | 211 |
| abstract_inverted_index.evaluated | 119 |
| abstract_inverted_index.increased | 196 |
| abstract_inverted_index.integrity | 84 |
| abstract_inverted_index.metabolic | 97, 242 |
| abstract_inverted_index.molecular | 44 |
| abstract_inverted_index.profiling | 98 |
| abstract_inverted_index.rationale | 284 |
| abstract_inverted_index.real-time | 105 |
| abstract_inverted_index.responses | 64 |
| abstract_inverted_index.staining, | 89, 95 |
| abstract_inverted_index.syngeneic | 161 |
| abstract_inverted_index.treatment | 8, 24 |
| abstract_inverted_index.viability | 82 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.Expression | 140 |
| abstract_inverted_index.associated | 233 |
| abstract_inverted_index.expression | 103 |
| abstract_inverted_index.orthotopic | 162 |
| abstract_inverted_index.predictive | 251 |
| abstract_inverted_index.prognostic | 249 |
| abstract_inverted_index.resistance | 19 |
| abstract_inverted_index.sensitizes | 27 |
| abstract_inverted_index.short-term | 50, 293 |
| abstract_inverted_index.silencing. | 109 |
| abstract_inverted_index.starvation | 51 |
| abstract_inverted_index.treatment. | 305 |
| abstract_inverted_index.Conclusions | 272 |
| abstract_inverted_index.ameliorates | 38 |
| abstract_inverted_index.association | 203 |
| abstract_inverted_index.compromised | 235 |
| abstract_inverted_index.enhancement | 231 |
| abstract_inverted_index.hypocaloric | 263 |
| abstract_inverted_index.integration | 122 |
| abstract_inverted_index.mechanistic | 169 |
| abstract_inverted_index.respiration | 237 |
| abstract_inverted_index.restriction | 295 |
| abstract_inverted_index.significant | 247 |
| abstract_inverted_index.therapeutic | 290 |
| abstract_inverted_index.Chemotherapy | 2 |
| abstract_inverted_index.Furthermore, | 253 |
| abstract_inverted_index.differential | 63 |
| abstract_inverted_index.establishing | 158 |
| abstract_inverted_index.mechanism(s) | 45 |
| abstract_inverted_index.restrictions | 22 |
| abstract_inverted_index.significance | 112 |
| abstract_inverted_index.(quantitative | 104 |
| abstract_inverted_index.CT-associated | 39 |
| abstract_inverted_index.iRNA-mediated | 108 |
| abstract_inverted_index.mitochondrial | 236 |
| abstract_inverted_index.tumor-bearing | 164 |
| abstract_inverted_index.Genome-phenome | 136 |
| abstract_inverted_index.characterized. | 60 |
| abstract_inverted_index.metabolomics), | 101 |
| abstract_inverted_index.susceptibility | 178 |
| abstract_inverted_index.transcriptomic | 124 |
| abstract_inverted_index.bioinformatical | 121 |
| abstract_inverted_index.preconditioning | 173 |
| abstract_inverted_index.translatability | 151 |
| abstract_inverted_index.chemotherapeutic | 34 |
| abstract_inverted_index.immunofluorescence), | 96 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 97 |
| corresponding_author_ids | https://openalex.org/A5023436565, https://openalex.org/A5088922536 |
| countries_distinct_count | 4 |
| institutions_distinct_count | 23 |
| corresponding_institution_ids | https://openalex.org/I200777214, https://openalex.org/I90267481 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/14 |
| sustainable_development_goals[0].score | 0.6100000143051147 |
| sustainable_development_goals[0].display_name | Life below water |
| citation_normalized_percentile.value | 0.98275693 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |