Abstract 4990: PP2A signaling is overridden by MEK/ERK activity leading to suppression of Bim and protection of melanoma cells from ER stress-induced apoptosis

2012 ◽  
Author(s):  
Kwang Hong Tay ◽  
Hsin-Yi Tseng ◽  
Lei Jing ◽  
Chen Chen Jiang ◽  
Yan Ye ◽  
...  
Keyword(s):  
Er Stress ◽  
Melanoma Cells ◽  
Induced Apoptosis ◽  
Erk Activity

scholarly journals Polyphenol-rich extract induces apoptosis with immunogenic markers in melanoma cells through the ER stress-associated kinase PERK

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Karol Prieto ◽  
Yu Cao ◽  
Eslam Mohamed ◽  
Jimena Trillo-Tinoco ◽  
Rosa A. Sierra ◽  
...  
Keyword(s):  
Er Stress ◽  
Stress Responses ◽  
Calcium Release ◽  
Melanoma Cells ◽  
Melanoma Tumor ◽  
Cancer Cell Death ◽  
Extracellular Release ◽  
Induced Apoptosis ◽  
Stress Mediators

Abstract Polyphenols elicit antitumor activities, in part, through the induction of anti- or pro-oxidant effects in cancer cells which promote priming of protective anti-tumor immunity. We recently characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) that stimulates in vivo antitumor responses against breast and melanoma tumor models via the promotion of immunogenic cancer cell death (ICD). However, the primary mediators whereby P2Et promotes ICD remained unknown. Here, we sought to elucidate the role that severe endoplasmic reticulum (ER) stress plays in mediating P2Et-induced apoptosis and ICD in murine melanoma cells. Our findings demonstrate a substantial selective induction of specific ER-stress mediators in B16-F10 melanoma cells treated with P2Et. While knockout of the ER stress-associated PKR-like ER kinase (PERK) prevented induction of apoptosis and expression of ICD markers in P2Et-treated cells, deletion of X-box binding protein 1 (Xbp1) did not. P2Et-driven activation of PERK in melanoma cells was found to promote ER-calcium release, disrupt mitochondrial membrane potential, and trigger upregulation of ICD drivers, surface calreticulin expression, and extracellular release of ATP and HMGB1. Notably, calcium release inhibition, but not targeting of PERK-driven integrated stress responses, prevented P2Et-induced apoptosis. Collectively, these results underline the central role of PERK-directed calcium release in mediating the antitumor and immunogenic actions of P2Et in melanoma cells.

IDH1, a CHOP and C/EBPβ-responsive gene under ER stress, sensitizes human melanoma cells to hypoxia-induced apoptosis

2015 ◽  
Vol 365 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Xuejun Yang ◽  
Tongde Du ◽  
Xiang Wang ◽  
Yingqiu Zhang ◽  
Wanglai Hu ◽  
...  
Keyword(s):  
Er Stress ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cells ◽  
Responsive Gene ◽  
Induced Apoptosis

scholarly journals Imiquimod‐induced apoptosis of melanoma cells is mediated by ER stress‐dependent Noxa induction and enhanced by NF ‐κB inhibition

2016 ◽  
Vol 20 (2) ◽  
pp. 266-286 ◽  
Author(s):  
Abdelouahid El‐Khattouti ◽  
Denis Selimovic ◽  
Matthias Hannig ◽  
Erin B. Taylor ◽  
Zakaria Y. Abd Elmageed ◽  
...  
Keyword(s):  
Er Stress ◽  
Melanoma Cells ◽  
Induced Apoptosis ◽  
Stress Dependent

Pentoxifylline triggers autophagy via ER stress response that interferes with Pentoxifylline induced apoptosis in human melanoma cells

2016 ◽  
Vol 103 ◽  
pp. 17-28 ◽  
Author(s):  
Kapil Sharma ◽  
Mohammad Ishaq ◽  
Gaurav Sharma ◽  
Mohammad Aslam Khan ◽  
Rajesh Kumar Dutta ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Er Stress Response ◽  
Human Melanoma Cells ◽  
Induced Apoptosis

scholarly journals 5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1183
Author(s):  
Mst Mamuna Sharmin ◽  
Md Aminul Islam ◽  
Itsuki Yamamoto ◽  
Shin Taniguchi ◽  
Shinichi Yonekura
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Palmitic Acid ◽  
Er Stress ◽  
Aminolevulinic Acid ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Protective Effects ◽  
Bovine Mammary Epithelial Cells ◽  
Induced Apoptosis

The conservation of mammary gland physiology by maintaining the maximum number of mammary epithelial cells (MECs) is of the utmost importance for the optimum amount of milk production. In a state of negative energy balance, palmitic acid (PA) reduces the number of bovine MECs. However, there is no effective strategy against PA-induced apoptosis of MECs. In the present study, 5-aminolevulinic acid (5-ALA) was established as a remedial agent against PA-induced apoptosis of MAC-T cells (an established line of bovine MECs). In PA-treated cells, the apoptosis-related genes BCL2 and BAX were down- and upregulated, respectively. The elevated expression of major genes of the unfolded protein response (UPR), such as CHOP, a proapoptotic marker (C/EBP homologous protein), reduced the viability of PA-treated MAC-T cells. In contrast, 5-ALA pretreatment increased and decreased BCL2 and BAX expression, respectively. Moreover, cleaved caspase-3 protein expression was significantly reduced in the 5-ALA-pretreated group in comparison with the PA group. The downregulation of major UPR-related genes, including CHOP, extended the viability of MAC-T cells pretreated with 5-ALA and also reduced the enhanced intensity of the PA-induced expression of phospho-protein kinase R-like ER kinase. Moreover, the enhanced expression of HO-1 (antioxidant gene heme oxygenase) by 5-ALA reduced PA-induced oxidative stress (OxS). HO-1 is not only protective against OxS but also effective against ER stress. Collectively, these findings offer new insights into the protective effects of 5-ALA against PA-induced apoptosis of bovine MECs.

scholarly journals iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1446
Author(s):  
Tingting Jin ◽  
Jun Lin ◽  
Yingchao Gong ◽  
Xukun Bi ◽  
Shasha Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Er Stress ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

scholarly journals Carfilzomib in Combination with Bortezomib Enhances Apoptotic Cell Death in B16-F1 Melanoma Cells

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 153
Author(s):  
Min Seung Lee ◽  
So Hyun Lim ◽  
Ah-Ran Yu ◽  
Chi Yeon Hwang ◽  
Insug Kang ◽  
...  
Keyword(s):  
Er Stress ◽  
Dose Reduction ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Proteasome Inhibitors ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Melanoma Cells ◽  
Eif2α Phosphorylation ◽  
Pharmacological Interactions

Proteasome inhibitors, such as bortezomib (BZ) and carfilzomib (CFZ), have been suggested as treatments for various cancers. To utilize BZ and/or CFZ as effective therapeutics for treating melanoma, we studied their molecular mechanisms using B16-F1 melanoma cells. Flow cytometry of Annexin V-fluorescein isothiocyanate-labeled cells indicated apoptosis induction by treatment with BZ and CFZ. Apoptosis was evidenced by the activation of various caspases, including caspase 3, 8, 9, and 12. Treatment with BZ and CFZ induced endoplasmic reticulum (ER) stress, as indicated by an increase in eIF2α phosphorylation and the expression of ER stress-associated proteins, including GRP78, ATF6α, ATF4, XBP1, and CCAAT/enhancer-binding protein homologous protein. The effects of CFZ on ER stress and apoptosis were lower than that of BZ. Nevertheless, CFZ and BZ synergistically induced ER stress and apoptosis in B16-F1 cells. Furthermore, the combinational pharmacological interactions of BZ and CFZ against the growth of B16-F1 melanoma cells were assessed by calculating the combination index and dose-reduction index with the CompuSyn software. We found that the combination of CFZ and BZ at submaximal concentrations could obtain dose reduction by exerting synergistic inhibitory effects on cell growth. Moreover, this drug combination reduced tumor growth in C57BL/6 syngeneic mice. Taken together, these results suggest that CFZ in combination with BZ may be a beneficial and potential strategy for melanoma treatment.

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