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Open AccessArticle

Estrogen Signaling Induces Mitochondrial Dysfunction-Associated Autophagy and Senescence in Breast Cancer Cells

1
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, UAE
2
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE
3
Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, UAE
*
Author to whom correspondence should be addressed.
Biology 2020, 9(4), 68; https://doi.org/10.3390/biology9040068
Received: 14 February 2020 / Revised: 13 March 2020 / Accepted: 25 March 2020 / Published: 1 April 2020
Previous work has shown that although estrogen (E2) disrupts cellular iron metabolism and induces oxidative stress in breast and ovarian cancer cells, it fails to induce apoptosis. However, E2 treatment was reported to enhance the apoptotic effects of doxorubicin in cancer cells. This suggests that E2 can precipitate anti-growth effects that render cancer cells more susceptible to chemotherapy. To investigate such anti-growth non-apoptotic, effects of E2 in cancer cells, MDA-MB-231 and MCF-7 cells were evaluated for the expression of key autophagy and senescence markers and for mitochondrial damage following E2 treatment. Treated cells experienced mitochondrial membrane depolarization along with increased expression of LC3-I/II, Pink1 and LAMP2, increased LC3-II accumulation and increased lysosomal and mitochondrial accumulation and flattening. E2-treated MCF-7 cells also showed reduced P53 and pRb780 expression and increased Rb and P21 expression. Increased expression of the autophagy markers ATG3 and Beclin1 along with increased levels of β-galactosidase activity and IL-6 production were evident in E2-treated MCF-7 cells. These findings suggest that E2 precipitates a form of mitochondrial damage that leads to cell senescence and autophagy in breast cancer cells. View Full-Text
Keywords: Estrogen; senescence; MCF-7; MDA-MB-231; mitochondria; autophagy Estrogen; senescence; MCF-7; MDA-MB-231; mitochondria; autophagy
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Bajbouj, K.; Shafarin, J.; Taneera, J.; Hamad, M. Estrogen Signaling Induces Mitochondrial Dysfunction-Associated Autophagy and Senescence in Breast Cancer Cells. Biology 2020, 9, 68.

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