Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells

Arij Fouzat; Ola Jihad Hussein; Ishita Gupta; Halema F Al-Farsi; Ashraf Khalil; Ala-Eddin Al Moustafa

doi:10.3389/fnut.2022.871667

Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells

Front Nutr. 2022 Mar 18:9:871667. doi: 10.3389/fnut.2022.871667. eCollection 2022.

Authors

Arij Fouzat¹, Ola Jihad Hussein¹, Ishita Gupta², Halema F Al-Farsi², Ashraf Khalil¹, Ala-Eddin Al Moustafa^{2

3}

Affiliations

¹ College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
² College of Medicine, QU Health, Qatar University, Doha, Qatar.
³ Biomedical Research Centre, Qatar University, Doha, Qatar.

Abstract

Elaeagnus angustifolia (EA) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40-50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA-treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC.

Keywords: Elaeagnus angustifolia; apoptosis; p53; stat3; triple-negative breast cancer.