Ester derivatives of salinomycin efficiently eliminate breast cancer cells via ER-stress-induced apoptosis

2021 ◽  
Vol 893 ◽  
pp. 173824
Author(s):  
Dominika Kuran ◽  
Sylwia Flis ◽  
Michał Antoszczak ◽  
Marlena Piskorek ◽  
Adam Huczyński
Keyword(s):  
Breast Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Induced Apoptosis ◽  
Derivatives Of

scholarly journals MAG-DHA Induces Apoptosis and Autophagy in Breast Cancer Cells via Lipid Peroxidation-Mediated Endoplasmic Reticulum Stress

2020 ◽  
Author(s):  
Jin-jie Zhang ◽  
Yong Yang ◽  
Feng Wang ◽  
Wen-ge Yang ◽  
Zuquan zou
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Docosahexaenoic Acid ◽  
Er Stress ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Induced Apoptosis

Abstract Background: Epidemiologic and pre-clinical studies have shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Previous studies found that docosahexaenoic acid monoglyceride (MAG-DHA) does not required pancreatic lipase to be absorbed, unlike DHA-triglyceride which needs to be hydrolyzed by sn-1,3’ specific gastric and (colipase-dependent) pancreatic lipases as free fatty acids and monoglycerol prior to intestinal absorption. Therefore, this property confers increased absorption, and thus a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol (TAG-DHA), or DHA-ethyl ester (EE-DHA). However, the anti-cancer actions of n-3 PUFA monoglyceride on breast cancer remain to be assessed.Methods: SKBR3 and E0771 cells were exposed in vitro to MAG-DHA. Cell viability (by MTT), malondialdehyde (MDA) levels, cell apoptosis and autophagy (by western blot), Beclin1 knockout (by siRNA) was examined. Transmission electron microscopy (TEM) was used for analyzing cell apoptosis and autophagy in vivo breast cancer exnografts. Results: In this study, we showed that docosahexaenoic acid monoglyceride (MAG-DHA) caused oxidative stress as evidenced by MDA accumulation, which triggered endoplasmic reticulum (ER) stress and subsequently induced apoptosis in E0771 and SKBR3 breast cancer cells. In particular, MAG-DHA-induced apoptosis is associated with the activation of the PERK-eIF2α pathway and caspase-12. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, by ER-stress-induced cell apoptosis. In addition, we found that MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Conclusions: Together, our data suggested that MAG-DHA combined with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

2021 ◽  
pp. 096032712110214
Author(s):  
Yansong Chen ◽  
Ye Tian ◽  
Gongsheng Jin ◽  
Zhen Cui ◽  
Wei Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glutamine Metabolism ◽  
Down Regulation ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

Notch4 Signaling Confers Susceptibility to TRAIL-Induced Apoptosis in Breast Cancer Cells

2015 ◽  
Vol 116 (7) ◽  
pp. 1371-1380 ◽  
Author(s):  
Shambhavi Naik ◽  
Marion MacFarlane ◽  
Apurva Sarin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Induced Apoptosis

Involvement of JNK/p73/NOXA in vitamin E analog-induced apoptosis of human breast cancer cells

2008 ◽  
Vol 47 (6) ◽  
pp. 436-445 ◽  
Author(s):  
Pei Wang ◽  
Weiping Yu ◽  
Zhanzhi Hu ◽  
Li Jia ◽  
Vishwanath R. Iyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin E ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Induced Apoptosis

scholarly journals Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

2004 ◽  
Vol 15 (7) ◽  
pp. 3266-3284 ◽  
Author(s):  
Romaine Ingrid Fernando ◽  
Jay Wimalasena
Keyword(s):  
Breast Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Dominant Negative ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Estrogens such as 17-β estradiol (E2) play a critical role in sporadic breast cancer progression and decrease apoptosis in breast cancer cells. Our studies using estrogen receptor-positive MCF7 cells show that E2 abrogates apoptosis possibly through phosphorylation/inactivation of the proapoptotic protein BAD, which was rapidly phosphorylated at S112 and S136. Inhibition of BAD protein expression with specific antisense oligonucleotides reduced the effectiveness of tumor necrosis factor-α, H2O2, and serum starvation in causing apoptosis. Furthermore, the ability of E2 to prevent tumor necrosis factor-α-induced apoptosis was blocked by overexpression of the BAD S112A/S136A mutant but not the wild-type BAD. BAD S112A/S136A, which lacks phosphorylation sites for p90RSK1 and Akt, was not phosphorylated in response to E2 in vitro. E2 treatment rapidly activated phosphatidylinositol 3-kinase (PI-3K)/Akt and p90RSK1 to an extent similar to insulin-like growth factor-1 treatment. In agreement with p90RSK1 activation, E2 also rapidly activated extracellular signal-regulated kinase, and this activity was down-regulated by chemical and biological inhibition of PI-3K suggestive of cross talk between signaling pathways responding to E2. Dominant negative Ras blocked E2-induced BAD phosphorylation and the Raf-activator RasV12T35S induced BAD phosphorylation as well as enhanced E2-induced phosphorylation at S112. Chemical inhibition of PI-3K and mitogen-activated protein kinase kinase 1 inhibited E2-induced BAD phosphorylation at S112 and S136 and expression of dominant negative Ras-induced apoptosis in proliferating cells. Together, these data demonstrate a new nongenomic mechanism by which E2 prevents apoptosis.

Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

2022 ◽  
Vol 12 (2) ◽  
pp. 273-278
Author(s):  
Daqing Jiang ◽  
Xianxin Xie ◽  
Cong Wang ◽  
Weijie Li ◽  
Jianjun He
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Signaling Activation

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

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