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

Overview

Journal Nutrients

Date 2024 Sep 28

PMID 39339789

Authors

Itzen Aguiniga-Sanchez

Edgar Ledesma-Martinez

Mariana Vazquez-Guerrero

David Hernandez-Alvarez

Amanda Velasco-Garcia

Katia Michell Rodriguez-Teran

Daniel Romero-Trejo

Victor Manuel Mendoza-Nunez

Victor Manuel Macias-Zaragoza

Edelmiro Santiago-Osorio

Affiliations

Soon will be listed here.

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.

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