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Exploring the Immunomodulatory Effects of Liposomal Daunorubicin on Jurkat Cells: A Study of Apoptosis and Gene Expression in Co-Cultured Mda-Mb-231 Cells Publisher



Mk Shanan Malik KAREEM ; A Arasteh AMIR ; Mm Mohammadamoli Mahsa MOHAMMAD ; M Ebrahimi MEHDI
Authors

Source: Pharmaceutical Sciences Published:2025


Abstract

Background: Breast cancer represents a significant aspect of women’s health, constituting approximately 30% of cancers affecting them globally, with a mortality rate of around 15%. In the quest for healing, immunotherapy has emerged as a beacon of hope, employing our body’s innate defenses to confront cancer. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) acts as a guardian, regulating immune responses, while COX-1’s influence on inflammation and invasion in cancer is modest yet notable. This study aims to explore the immunomodulatory effects of liposomal daunorubicin (LipDau) on Jurkat cells, evaluating the cancer cell fate through apoptosis and the expression of CTLA-4 and COX-1 genes in MDA-MB-231 cells as they co-exist with Jurkat cells. Methods: We assessed cell cytotoxicity in MDA-MB-231 cells under various treatments using the MTT assay. The apoptosis process was traced through flow cytometry, comparing controls, LipDau treatments, Jurkat cells, and activated Jurkat cells. The expression of CTLA-4 and COX-1 genes in MDA-MB-231 cells was measured through real-time PCR across similar treatments. Results: The application of LipDau, particularly in the presence of activated Jurkat cells, led to a significant decline in MDA-MB-231 cells, correlating with LipDau concentrations. Activated Jurkat cells demonstrated a lower IC50 than LipDau (21.5 and 31.1 μM, respectively). Notably, apoptosis rates rose sharply in MDA-MB-231 cells co-cultured with Jurkat cells at IC50 concentrations of LipDau, accompanied by decreased expression of CTLA-4 and COX-1 genes following treatment. Conclusion: Through the nurturing guidance of LipDau-activated Jurkat cells, a protective response emerged against tumor cells in MDA-MB-231, moderated by the CTLA-4 checkpoint and a suppression of inflammatory pathways via COX-1. These interactions facilitated the journey towards apoptosis and a halt in the relentless spread of metastatic breast cancer. © 2025 Elsevier B.V., All rights reserved.
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