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

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...

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Bibliographic Details
Published in:Biology (Basel, Switzerland) Switzerland), 2020-04, Vol.9 (4), p.68
Main Authors: Bajbouj, Khuloud, Shafarin, Jasmin, Taneera, Jalal, Hamad, Mawieh
Format: Article
Language:English
Subjects:
Apoptosis
Autophagy
Breast cancer
Cancer therapies
Cell cycle
Chemotherapy
Depolarization
Doxorubicin
Estrogen
Flow cytometry
Immunoglobulins
Interleukin 6
MCF-7
MDA-MB-231
Membrane potential
Metastasis
Mitochondria
Ovarian cancer
Oxidative metabolism
Oxidative stress
p53 Protein
Phagocytosis
Proteins
PTEN-induced putative kinase
Senescence
Software
Tumorigenesis
β-Galactosidase
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Summary: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.
ISSN:2079-7737
2079-7737
DOI:10.3390/biology9040068