Naglaa Khedr

Egypt

Luteolin Potentiate Doxorubicin Efficacy by Modulating MDR1, ABCG2, Cancer stem cells and Telomerase in Breast Cancer

Nahla E. El-Ashmawy1
Ghada M. Al-Ashmawy1
Omnia B. Hamada1
Naglaa F. Khedr 1
1- Tanta University, Faculty of Pharmacy, Department of Biochemistry, Egypt, Postal Code: 31527

Abstract

Background

Background: Multidrug resistance (MDR) limits the efficacy of breast cancer (BC) chemotherapy, that is often mediated by ATP-binding cassette (ABC) transporters, cancer stem cells (CSC) and telomerase activity. Objective: This study investigated the anticancer potential of luteolin (LUT), alone or in combination with doxorubicin (DOX), in non-resistant (MCF-7) BC cell lines and Adriamycin cancer resistant cell lines (MCF-7/ADR).

Methods

Methods: Cells were treated with DOX, LUT, or combinations (LUT+DOX) for 48 h. Cytotoxicity (MTT assay), apoptosis, cell cycle, and CSC populations (CD44⁺/CD24⁻) were evaluated by flow cytometry. MDR1 and ABCG2 expression and telomerase activity were determined by RT-qPCR

Results

Results: All treatments decreased viability, induced apoptosis, and arrested the cell cycle in a dose-dependent manner. Lut+DOX synergistically enhanced DOX cytotoxicity, downregulated MDR1 and ABCG2, reduced CSCs, and inhibited telomerase activity in MCF-7 BC cells. LUT+DOX showed strong anti-CSC effects in MCF-7 cells than in MCF-7/ADR resistant cells.

Conclusions

Conclusion: LUT alone or combined with DOX enhances chemosensitivity and suppresses MDR-related mechanisms, offering a potential therapeutic strategy to overcome drug resistance in BC.