Itzen Aguiñiga-Sánchez, Edgar Ledesma-Martínez, Mariana Vázquez-Guerrero, David Hernández-Álvarez, Amanda Velasco-García, Katia Michell Rodríguez-Terán, Daniel Romero-Trejo, Víctor Manuel Mendoza-Núñez, Víctor Manuel Macías-Zaragoza, Edelmiro Santiago-Osorio
{"title":"Antineoplastic Activity of Sodium Caseinate in a Cytarabine-Resistant Mouse Acute Myeloid Leukemia Cell Line.","authors":"Itzen Aguiñiga-Sánchez, Edgar Ledesma-Martínez, Mariana Vázquez-Guerrero, David Hernández-Álvarez, Amanda Velasco-García, Katia Michell Rodríguez-Terán, Daniel Romero-Trejo, Víctor Manuel Mendoza-Núñez, Víctor Manuel Macías-Zaragoza, Edelmiro Santiago-Osorio","doi":"10.3390/nu16183190","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematological neoplasm of rapid and progressive onset, and is the most common form of leukemia in adults. Chemoresistance to conventional treatments such as cytarabine (Ara-C) and daunorubicin is a main cause of relapse, recurrence, metastasis, and high mortality in AML patients. It is known that sodium caseinate (SC), a salt derived from casein, a milk protein, inhibits growth and induces apoptosis in acute myeloid leukemia cells but not in normal hematopoietic cells. However, it is unknown whether SC retains its antileukemic effect in cytarabine-resistant AML cell lines.</p><p><strong>Objective: </strong>To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models.</p><p><strong>Methods: </strong>The SC inhibits the growth and induces apoptosis in parental WEHI-3 AML cells. Here, we generated two cytarabine-resistant sublines, WEHI-CR25 and WEHI-CR50, which exhibit 6- and 16-fold increased resistance to cytarabine, respectively, compared to the parental WEHI-3 cells. Thus, these sublines mimic a chemoresistant model.</p><p><strong>Results: </strong>We demonstrate that WEHI-CR25 and WEHI-CR50 cells retain sensitivity to SC, similar to parental WEHI-3 cells. This sensitivity results in inhibited cell proliferation, induced apoptosis, and increased expression of ENT1 and dCK, molecules involved in the entry and metabolism of Ara-C, while decreasing MDR1 expression. Additionally, we observed that SC prolonged the survival of WEHI-CR50 tumor-bearing mice, despite their resistance to Ara-C.</p><p><strong>Conclusion: </strong>This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells.</p>","PeriodicalId":19486,"journal":{"name":"Nutrients","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435215/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrients","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/nu16183190","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Acute myeloid leukemia (AML) is a hematological neoplasm of rapid and progressive onset, and is the most common form of leukemia in adults. Chemoresistance to conventional treatments such as cytarabine (Ara-C) and daunorubicin is a main cause of relapse, recurrence, metastasis, and high mortality in AML patients. It is known that sodium caseinate (SC), a salt derived from casein, a milk protein, inhibits growth and induces apoptosis in acute myeloid leukemia cells but not in normal hematopoietic cells. However, it is unknown whether SC retains its antileukemic effect in cytarabine-resistant AML cell lines.
Objective: To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models.
Methods: The SC inhibits the growth and induces apoptosis in parental WEHI-3 AML cells. Here, we generated two cytarabine-resistant sublines, WEHI-CR25 and WEHI-CR50, which exhibit 6- and 16-fold increased resistance to cytarabine, respectively, compared to the parental WEHI-3 cells. Thus, these sublines mimic a chemoresistant model.
Results: We demonstrate that WEHI-CR25 and WEHI-CR50 cells retain sensitivity to SC, similar to parental WEHI-3 cells. This sensitivity results in inhibited cell proliferation, induced apoptosis, and increased expression of ENT1 and dCK, molecules involved in the entry and metabolism of Ara-C, while decreasing MDR1 expression. Additionally, we observed that SC prolonged the survival of WEHI-CR50 tumor-bearing mice, despite their resistance to Ara-C.
Conclusion: This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells.
期刊介绍:
Nutrients (ISSN 2072-6643) is an international, peer-reviewed open access advanced forum for studies related to Human Nutrition. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.