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. 2022 Sep;49(9):8777-8784.
doi: 10.1007/s11033-022-07727-0. Epub 2022 Jul 8.

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

Marwah Suliman Maashi  1 , Mahmood Al-Mualm  2 , Ghaidaa Raheem Lateef Al-Awsi  3 , Maria Jade Catalan Opulencia  4 , Moaed E Al-Gazally  5 , Bekhzod Abdullaev  6 , Walid Kamal Abdelbasset  7   8 , Mohammad Javed Ansari  9 , Abduladheem Turki Jalil  10 , Fahad Alsaikhan  11 , Mohammed Nader Shalaby  12 , Yasser Fakri Mustafa  13
Affiliations

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

Marwah Suliman Maashi et al. Mol Biol Rep. 2022 Sep.

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.

Keywords: Apigenin; Breast cancer resistance; Doxorubicin; JAK2; MDR-1; STAT3.

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References

    1. Tungsukruthai S, Petpiroon N, Chanvorachote P (2018) Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds. Anticancer Res 38:2607–2618. https://doi.org/10.21873/anticanres.12502 - DOI - PubMed
    1. Brook N, Brook E, Dharmarajan A, Dass CR, Chan A (2018) Breast cancer bone metastases: pathogenesis and therapeutic targets. Int J Biochem Cell Biol 96:63–78. https://doi.org/10.1016/j.biocel.2018.01.003 - DOI - PubMed
    1. Waks AG, Winer EP (2019) Breast Cancer Treatment: A Review. JAMA 321:288–300. https://doi.org/10.1001/jama.2018.19323 - DOI - PubMed
    1. Cai S, Thati S, Bagby TR, Diab HM, Davies NM, Cohen MS, Forrest ML (2010) Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer. J Control Release 146:212–218. https://doi.org/10.1016/j.jconrel.2010.04.006 - DOI - PubMed - PMC
    1. Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, Altman RB (2011) Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics 21:440–446. https://doi.org/10.1097/FPC.0b013e32833ffb56 - DOI - PubMed - PMC

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