1. Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway.
- Author
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Maashi MS, Al-Mualm M, Al-Awsi GRL, Opulencia MJC, Al-Gazally ME, Abdullaev B, Abdelbasset WK, Ansari MJ, Jalil AT, Alsaikhan F, Shalaby MN, and Mustafa YF
- Subjects
- Apoptosis, Cell Line, Tumor, Doxorubicin pharmacology, Doxorubicin therapeutic use, Drug Resistance, Neoplasm genetics, Female, Humans, MCF-7 Cells, Signal Transduction, Apigenin pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms metabolism
- Abstract
Background: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells., Methods: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting., Results: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines., Conclusions: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2022
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