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

Abstract

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.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis

“…Researchers in UAE have investigated the apoptotic effects of various compounds on cancer cells. Researchers have found that these compounds induce apoptotic cell death in cancer cells, as evidenced by various markers such as MTT assay, DNA ladder formation, and induction of p53 protein [ [57] , [58] , [59] ]. The exploration of novel cancer therapeutics is of great significance in many nations.…”

“…By utilizing high-frequency sound waves, ultrasound can enhance drug penetration into tumors, trigger drug release from delivery systems, and improve cellular uptake. UCR aims to optimize the therapeutic outcomes of doxorubicin and chemotherapy by exploring innovative drug delivery systems and ultrasound parameters [ 57 , [60] , [61] , [62] , [63] , [64] ]. The ultimate goal is to improve targeted drug delivery, enhance the efficacy of doxorubicin, and mitigate its side effects, thereby advancing cancer therapy.…”

Mechanisms of Senescence in Cancer: Positive and Negative Aspects of Cancer Cells Senescence

“…However, recent data indicated the role of E2 in breast cancer senescence. Studies by Bajbouj et al (2020) showed that E2 treatment of MCF-7 and MDA-MB-231 breast cancer cells reduced expression of p53, increased expression of p21 and LC3, presence of senescence-associated heterochromatin foci and higher levels of SA-βgalactosidase activity [202].…”