{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:21:14Z","timestamp":1767244874929,"version":"3.48.0"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil","award":["001"],"award-info":[{"award-number":["001"]}]},{"DOI":"10.13039\/501100003593","name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["408347\/2025-2"],"award-info":[{"award-number":["408347\/2025-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["305434\/2025-0"],"award-info":[{"award-number":["305434\/2025-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Piau\u00ed"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Oncological treatment remains a major clinical challenge. Despite therapeutic advances and the diversity of available approaches, many tumors continue to exhibit limited responsiveness to chemotherapy. In this context, nutrition has emerged as a promising complementary strategy to support cancer therapy. In particular, interventions based on nutritional deprivation have gained prominence due to their ability to modulate tumor metabolism, inducing alterations that may increase the sensitivity of cancer cells to conventional treatments. Accordingly, the present study aimed to evaluate the safety and efficacy of caloric restriction combined with chemotherapy in a Sarcoma-180 model, investigating its effects on immunological and hematological parameters, antioxidant activity, oxidative stress, and tumor and liver morphology, as well as DNA damage. Methods: Mice bearing Sarcoma-180 were randomly assigned to four groups: Ad Libitum (AL), Ad Libitum + Doxorubicin (ALDOX), Caloric Restriction (CR), and Caloric Restriction + Doxorubicin (CRDOX). Assessment included tumor weight and volume, food and caloric intake, hematotoxicity, lipid metabolism, oxidative stress and antioxidant markers, genotoxicity, morphological alterations in the tumor and liver, and overall survival. Results: The data obtained demonstrate that caloric restriction combined with doxorubicin is both safe and feasible, as it preserves body weight and does not induce metabolic disturbances. Importantly, this combined strategy produced a marked reduction in tumor volume and mass while also mitigating the hematotoxicity typically associated with doxorubicin. In peripheral blood, the regimen decreased chemotherapy-induced DNA damage, supporting a systemic protective effect. Consistently, the combination reduced oxidative stress markers (NOx and MDA) and enhanced antioxidant activity within the tumor. Histological analyses further confirmed these outcomes, showing tumor cell death with features compatible with apoptosis and reduced local invasion. Together, these data indicate that caloric restriction enhances the antitumor efficacy of doxorubicin while simultaneously improving treatment tolerance. Conclusions: This study demonstrates that caloric restriction, combined with doxorubicin, is safe, well-tolerated, and enhances the antitumor response in the Sarcoma-180 model.<\/jats:p>","DOI":"10.3390\/cancers18010110","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caloric Restriction Enhances Chemotherapy Efficacy and Reshapes Stress Responses in Sarcoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-0719","authenticated-orcid":false,"given":"Jorddam Almondes","family":"Martins","sequence":"first","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irislene Costa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Sousa","family":"Reinaldo","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dallyla Jennifer Morais de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-1020","authenticated-orcid":false,"given":"Isabelle Vasconcelos","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz de Mello Pereira","family":"Rego","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8131-4364","authenticated-orcid":false,"given":"Aureliano Machado de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-4625","authenticated-orcid":false,"given":"Taline Alves","family":"Nobre","sequence":"additional","affiliation":[{"name":"Toxicological Genetics Research Laboratory (LAPGENIC), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-4320","authenticated-orcid":false,"given":"Athanara Alves de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Toxicological Genetics Research Laboratory (LAPGENIC), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Pedro Alves Damasceno do","family":"Lago","sequence":"additional","affiliation":[{"name":"Toxicological Genetics Research Laboratory (LAPGENIC), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rayran Walter Ramos de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cancerology (LABCANCER), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego Pereira de","family":"Menezes","sequence":"additional","affiliation":[{"name":"Laboratory of Antineoplastic Pharmacology (LAFAN), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alda C\u00e1ssia Alves da","family":"Silva","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalton","family":"Dittz","sequence":"additional","affiliation":[{"name":"Laboratory of Antineoplastic Pharmacology (LAFAN), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana Maria Viana","family":"Nunes","sequence":"additional","affiliation":[{"name":"Pathology and Histology Laboratory (LaPaH), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3109-7899","authenticated-orcid":false,"given":"Vladimir Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Genomic Surveillance and Molecular Biology Laboratory, Oswaldo Cruz Foundation, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-7871","authenticated-orcid":false,"given":"Juliana Soares","family":"Severo","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, 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Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-1482","authenticated-orcid":false,"given":"Jo\u00e3o Marcelo de Castro","family":"e Sousa","sequence":"additional","affiliation":[{"name":"Toxicological Genetics Research Laboratory (LAPGENIC), Department of Biochemistry and Pharmacology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-7458","authenticated-orcid":false,"given":"Francisco Leonardo","family":"Torres-Leal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piau\u00ed, Teresina 64049-550, PI, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41568-020-0266-x","article-title":"Key steps for effective breast cancer prevention","volume":"20","author":"Britt","year":"2020","journal-title":"Nat. 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