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.

scholarly journals Docosahexaenoic acid monoglyceride induces apoptosis and autophagy in breast cancer cells via lipid peroxidation-mediated endoplasmic reticulum stress

2021 ◽  
Author(s):  
Tian-tian Wang ◽  
Yong Yang ◽  
Feng Wang ◽  
Wen-ge Yang ◽  
Jin-jie Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Docosahexaenoic Acid ◽  
Growth Inhibition ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Mcf 7

Abstract Epidemiologic and pre-clinical studies have shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride (MAG-DHA), a docosahexaenoic acid sn-1-monoacylglyceroldoes not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol, or DHA-ethyl ester. However, the anti-cancer actions and underlying mechanisms of MAG-DHA on breast cancer remain to be assessed. In this study, MAG-DHA induced significant growth inhibition in MCF-7 and MDA-MB-231 breast cancer cells in a dose-dependent manner. MAG-DHA treatment (80μM) led to 83.8% and 94.3% growth inhibition between MCF-7 and MDA-MB-231 cells, respectively. MAG-DHA-induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase-3, poly (ADP-ribose) polymerase (PARP) and caspase-12. In particular, MAG-DHA-induced apoptosis was triggered by oxidative stress-mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK-eIF2α pathway in ER. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG-DHA group (0.271 cm3) and control group (0.875cm3) after 15 daily MAG-DHA treatments. The in vitro anti-breast cancer mechanism of MAG-DHA was supported by the in vivo xenograft model. In addition, 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. Our data suggested that MAG-DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.

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 Autocrine Growth Hormone (GH)-Mediated Triptolide Resistance Overcame by Metformin Co-Treatment in MDA-MB231 Breast Cancer Cells Through ER Stress Pathway

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 9
Author(s):  
Amani Abdulmunem ◽  
Pınar Obakan-Yerlikaya ◽  
Elif-Damla Arisan ◽  
Ajda Coker-Gurkan
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autocrine Growth ◽  
Common Cancer

Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells.

scholarly journals High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells

2017 ◽  
Vol 95 (2) ◽  
pp. 289-294 ◽  
Author(s):  
Ali Burak Ozkaya ◽  
Handan Ak ◽  
Hikmet Hakan Aydin
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Survival Function ◽  
Active Form ◽  
Breast Cancer Cell Lines ◽  
Transcriptomic Profile

Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.

scholarly journals Atiprimod Triggered Apoptotic Cell Death via Acting on PERK/eIF2a/ATF4/CHOP and STAT3/NF-KB axis in MDA-MB-231 and MDA-MB-468 Breast Cancer Cells

2021 ◽  
Author(s):  
Ajda Coker-Gurkan ◽  
Esin Can ◽  
Semanur Sahin ◽  
PINAR OBAKAN YERLIKAYA ◽  
Elif-Damla ARISAN
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Tyrosine Kinases ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Pivotal Role ◽  
Type I ◽  
Stat3 Phosphorylation

Abstract Purpose: The constitutive activation of STAT3 through receptor tyrosine kinases triggered breast cancer cell growth, and invasion-metastasis. Atiprimod impacts anti-proliferative, anti-carcinogenic effects in hepatocellular carcinoma, lymphoma, multiple myeloma via hindering the biological activity of STAT3. Dose-dependent atiprimod evokes first autophagy as a survival mechanism and then apoptosis due to prolonged ER stress in pituitary adenoma cells. The therapeutic efficiency and mechanistic action of atiprimod in breast cancer cells have not been investigated yet. Thus, we aimed to modulate the pivotal role of ER stress in atiprimod-triggered apoptosis in MDA-MB-231 and MDA-MB-468 breast cancer cells. Results: Dose- and time-dependent atiprimod treatment inhibits cell viability and colony formation in MDA-MB-468 and MDA-MB-231 breast cancer cells. A moderate dose of atiprimod (2 mM) inhibited STAT3 phosphorylation at Tyr705 residue and also suppressed the total expression level of p65. In addition, nuclear localization of STAT1, 3 and NF-kB was prevented by atiprimod exposure in MDA-MB-231 and MDA-MB-468 cells. Atiprimod evokes PERK, BiP, ATF-4, CHOP upregulation, and PERK (Thr980), eIF2a (Ser51) phosphorylation’s. However, atiprimod suppressed IRE1a-mediated Atg-3, 5, 7, 12 protein expressions and no alteration were observed on Beclin-1, p62 expression levels. PERK/eIF2a/ATF4/CHOP axis pivotal role in atiprimod-mediated G1/S arrest and apoptosis via Bak, Bax, Bim and PUMA upregulation in MDA-MB-468 cells. Moreover, atiprimod renders MDA-MB-231 more vulnerable to type I programmed cell death by plasmid-mediated increased STAT3 expression. Conclusion: Atiprimod induced prolonged ER stress-mediated apoptosis via both activating PERK/eIF2a/ATF4/CHOP axis and suppressing STAT3/NF-kB transcription factors nuclear migration in TBNC cells.

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