Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway

• Published in: Molecular biology reports 2022-09, Vol.49 (9), p.8777-8784
• Main Authors: Maashi, Marwah Suliman, Al-Mualm, Mahmood, Al-Awsi, Ghaidaa Raheem Lateef, Opulencia, Maria Jade Catalan, Al-Gazally, Moaed E., Abdullaev, Bekhzod, Abdelbasset, Walid Kamal, Ansari, Mohammad Javed, Jalil, Abduladheem Turki, Alsaikhan, Fahad, Shalaby, Mohammed Nader, Mustafa, Yasser Fakri
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Breast cancer; Doxorubicin; Flavonoids; Gene expression; Histology; Janus kinase; Janus kinase 2; Kinases; Life Sciences; MDR1 protein; Morphology; Original Article; P-Glycoprotein; Phosphorylation; Signal transduction; Stat3 protein; Western blotting
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07727-0

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.