Antineoplastic Activity of Sodium Caseinate in a Cytarabine-Resistant Mouse Acute Myeloid Leukemia Cell Line

• Published in: Nutrients Vol. 16; no. 18; p. 3190
• Main Authors: Aguiñiga-Sánchez, Itzen, Ledesma-Martínez, Edgar, Vázquez-Guerrero, Mariana, Hernández-Álvarez, David, Velasco-García, Amanda, Rodríguez-Terán, Katia Michell, Romero-Trejo, Daniel, Mendoza-Núñez, Víctor Manuel, Macías-Zaragoza, Víctor Manuel, Santiago-Osorio, Edelmiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.09.2024; MDPI
• Subjects: acute myeloid leukemia; Analysis; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Cancer therapies; Care and treatment; Casein; Caseins - pharmacology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; chemoresistance; Chemotherapy; Clinical outcomes; Clinical trials; Cytarabine; Cytarabine - pharmacology; Drug Resistance, Neoplasm - drug effects; Health aspects; Kinases; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - pathology; Medical prognosis; Mice; milk protein; Physiological aspects; Sodium; sodium caseinate; Tumors; Mexico; St Louis Missouri; United States > US; Germany; apoptosis; chemoresistance; acute myeloid leukemia; sodium caseinate; milk protein
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16183190

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. To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models. 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. 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. This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells.