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

Abstract 590: Increased Endoplasmic Reticulum Stress in Atherosclerotic Plaques Associated With Acute Coronary Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masafumi Myoishi ◽  
Testuo Minamino ◽  
Masafumi Kitakaze
Keyword(s):  
Endoplasmic Reticulum ◽  
Coronary Artery ◽  
Er Stress ◽  
Atherosclerotic Plaques ◽  
Coronary Syndrome ◽  
Er Chaperone ◽  
Unstable Plaques ◽  
Induced Apoptosis ◽  
Stress Dependent ◽  
Dependent Pathway

Background Endoplasmic reticulum (ER) responds to various stresses by up-regulation of ER chaperones, and prolonged ER stress eventually causes apoptosis. Although apoptosis is considered to be essential for the progression and rupture of atherosclerotic plaques, the influence of ER stress and apoptosis on rupture of unstable coronary plaques remains unclear. Methods and Results We obtained 152 coronary artery segments at autopsy and 40 atherectomy specimens from 71 and 40 patients, respectively . Smooth muscle cells (SMCs) and macrophages in the fibrous caps of thin cap atheroma and ruptured plaques, but not in the fibrous caps of thick cap atheroma and fibrous plaques, showed a marked increase in the expression of ER chaperone and numbers of apoptotic cells. ER chaperones also expressed higher in atherectomy specimens from patients with unstable angina pectoris than with stable angina. To explore the plausible molecular mechanism of activation of ER stress and the mechanistic link to apoptosis, we investigated plaque lipids such as oxysterols. Among oxysterols, expression of 7-ketocholesterol was increased in the fibrous caps of thin cap atheroma compared with thick cap atheroma. Treatment of either cultured coronary artery SMCs or THP-1 cells with 7-ketocholesterol induced upregulation of ER chaperones and apoptosis, while these changes were prevented by antioxidants. We also investigated possible signaling pathways for ER-initiated apoptosis and found that the CHOP (a transcription factor induced by ER stress)-dependent pathway was activated in unstable plaques. In addition, knockdown of CHOP expression by siRNA decreased ER stress-dependent death of cultured coronary artery SMCs and THP-1 cells. Conclusions Increased ER stress occurs in unstable plaques. Our findings suggest that ER stress-induced apoptosis of SMCs and macrophages may contribute to plaque vulnerability.

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 15,16-Dihydrotanshinone I, a Compound ofSalvia miltiorrhizaBunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Mao-Te Chuang ◽  
Feng-Ming Ho ◽  
Chien-Chih Wu ◽  
Shao-Yu Zhuang ◽  
Shyr-Yi Lin ◽  
...  
Keyword(s):  
Er Stress ◽  
Prostate Carcinoma ◽  
Therapeutic Potential ◽  
Binding Protein ◽  
Salvia Miltiorrhiza ◽  
Carcinoma Cells ◽  
Initiation Factor ◽  
Human Prostate ◽  
Induced Apoptosis ◽  
Stress Dependent

5,16-dihydrotanshinone I (DHTS) is extracted fromSalvia miltiorrhizaBunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion

2011 ◽  
Vol 301 (4) ◽  
pp. H1471-H1486 ◽  
Author(s):  
Jianping Tao ◽  
Wei Zhu ◽  
Yapeng Li ◽  
Ping Xin ◽  
Jing Li ◽  
...  
Keyword(s):  
Er Stress ◽  
Signaling Pathways ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Erk Activation ◽  
Caspase 12 ◽  
Induced Apoptosis ◽  
Stress Dependent

Endoplasmic reticulum (ER) stress is activated during and contributes to ischemia-reperfusion (I/R) injury. Attenuation of ER stress-induced apoptosis protects the heart against I/R injury. Using apelin, a ligand used to activate the apelin APJ receptor, which is known to be cardioprotective, this study was designed to investigate 1) the time course of changes in I/R injury after ER stress; 2) whether apelin infusion protects the heart against I/R injury via modulation of ER stress-dependent apoptosis signaling pathways; and 3) how phosphatidylinositol 3-kinase (PI3K)/Akt, endothelial nitric oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and ERK activation are involved in the protection offered by apelin treatment. The results showed that, using an in vivo rat I/R model induced by 30 min of ischemia followed by reperfusion, infarct size (IS) increased from 2 h of reperfusion (34.85 ± 2.14%) to 12 h of reperfusion (48.98 ± 3.35, P < 0.05), which was associated with an abrupt increase in ER stress-dependent apoptosis activation, as evidenced by increased CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and JNK activation (CHOP: 2.49-fold increase, caspase-12: 2.09-fold increase, and JNK: 3.38-fold increase, P < 0.05, respectively). Administration of apelin at 1 μg/kg not only completely abolished the activation of ER stress-induced apoptosis signaling pathways at 2 h of reperfusion but also significantly attenuated time-related changes at 24 h of reperfusion. Using pharmacological inhibition, we also demonstrated that PI3K/Akt, AMPK, and ERK activation were involved in the protection against I/R injury via inhibition of ER stress-dependent apoptosis activation. In contrast, although eNOS activation played a role in decreasing IS at 2 h of reperfusion, it failed to modify either IS or ER stress-induced apoptosis signaling pathways at 24 h after reperfusion.

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
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