Abstract

Abbreviations CDK2 Cyclin-dependent kinase 2 DNA Deoxyribonucleic acid KD Knockdown KO Knock-out MAPK Mitogen-activated protein kinase PCNA Proliferating cell nuclear antigen PPARa Peroxisome proliferator-activated receptor alpha SREBF Sterol regulatory element-binding protein gene STS Short-term starvation WT Wild type Dear Editor, Short-term fasting (up to 48 hours) activates strong physiological and molecular responses [ 1]. MC38 murine colon cancer cells were sensitized to 100 μmol/L oxaliplatin toxicity by STS (Supplementary Figure S3A), and p21 knockdown prevented this enhancing effect (Supplementary Figure S3B-F). p53 protein expression followed the same trend in MC38 cells (Supplementary Figure S3C) than in human cells, although p53 was more strongly induced with STS in MC38 cells, which might explain their enhanced sensitization to oxaliplatin treatment. When tumors reached a certain size, the mice were divided into four treatment groups: (1) saline; (2) two cycles of 7.5 mg/kg oxaliplatin; (3) two cycles of 48 hours of fasting (24 hours before and 24 hours after saline inoculation); (4) two cycles of a combination of fasting and chemotherapy. p21-WT MC38 cells responded equally to oxaliplatin treatment than to 48 hours of fasting, as already shown for other cell types [ 7], and a combination of oxaliplatin and fasting induced the strongest effect (Figure 1C and Supplementary Figure S3G). To test if the critical role of p21 could be applied to chemotherapies different from oxaliplatin, we measured cell viability of colon cancer cell lines cultured in control or STS medium and treated with increasing concentrations of 5-fluorouracil (Supplementary Figure S4A), doxorubicin (Supplementary Figure S4B) or etoposide (Supplementary Figure S4C).

Details

Title
p21 is necessary for the beneficial effects of fasting during chemotherapy
Author
Plaza, Adrián 1   VIAFID ORCID Logo  ; Pastor-Fernández, Andrés 1   VIAFID ORCID Logo  ; López-Aceituno, José L 1   VIAFID ORCID Logo  ; Barradas, Marta 1   VIAFID ORCID Logo  ; Pantoja, Cristina 1   VIAFID ORCID Logo  ; Fernandez-Marcos, Pablo J 1   VIAFID ORCID Logo 

 Metabolic Syndrome Group (BIOPROMET), Madrid Institute for Advanced Studies (IMDEA) Food, Madrid, Spain 
Pages
164-168
Section
LETTERS TO THE EDITOR
Publication year
2023
Publication date
Jan 2023
Publisher
John Wiley & Sons, Inc.
e-ISSN
2523-3548
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2767337693
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.