Article
Cell Biology
Ruiyuan Xu, Jianlu Song, Rexiati Ruze, Yuan Chen, Xinpeng Yin, Chengcheng Wang, Yupei Zhao
Summary: This study reveals squalene epoxidase (SQLE) as a novel oncogene that promotes pancreatic cancer (PC) growth by mitigating endoplasmic reticulum stress and activating lipid raft-regulated Src/PI3K/Akt signaling pathway. SQLE facilitates cell proliferation, induces cell cycle progression, and inhibits apoptosis in vitro, while promoting tumor growth in vivo. SQLE inhibitors effectively suppress PC cell proliferation and xenograft tumor growth, highlighting the potential of SQLE as a therapeutic target for PC.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Michela Pecoraro, Adele Serra, Maria Pascale, Silvia Franceschelli
Summary: Correct protein folding is essential for cellular wellbeing, but accumulation of misfolded proteins in the endoplasmic reticulum (ER) can disrupt cellular homeostasis and cause ER stress. Protein misfolding has been implicated in various human diseases, including cancer, diabetes, and cystic fibrosis. The unfolded protein response (UPR) is activated in response to ER stress and involves the three ER-resident proteins, IRE1 alpha, PERK, and ATF6. This article highlights the importance of correct protein folding and the potential of the drug lumacaftor (Vx-809) in reducing ER stress and inflammation associated with protein misfolding. Rating: 8/10
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yixuan Zhang, Jianzhuang Wu, Yao Fu, Ranran Yu, Haochen Su, Qisi Zheng, Hao Wu, Siqi Zhou, Kun Wang, Jing Zhao, Shanshan Shen, Guifang Xu, Lei Wang, Chao Yan, Xiaoping Zou, Ying Lv, Shu Zhang
Summary: This study identified Hesperadin as a potent anti-cancer compound against pancreatic cancer (PC) by inhibiting cell growth and inducing apoptotic cell death. Mechanistic studies revealed that Hesperadin increased GADD45A expression via ATF4, leading to apoptosis. Immunohistochemical staining demonstrated the correlation between ATF4 and GADD45A expression. PC xenograft studies confirmed the inhibitory effect of Hesperadin on PC cell growth in vivo.
Article
Genetics & Heredity
Wang Xiao, Rong-Chang Cao, Wan-Jun Yang, Jie-Hui Tan, Ruo-Qi Liu, He-Ping Kan, Lei Zhou, Na Zhang, Zhi-Ye Chen, Xue-Mei Chen, Jia Xu, Guo-Wei Zhang, Peng Shen
Summary: This study aimed to investigate the prognostic value of endoplasmic reticulum (ER) stress-related and apoptosis-related genes in pancreatic cancer (PC) patients. The results demonstrated that upregulation of ATF6 and downregulation of EMC6 and APAF1 were associated with poor prognosis in PC patients, suggesting that these genes may serve as potential therapeutic targets.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Makoto Kawamoto, Shiro Kohi, Toshiya Abe, Mohamad Dbouk, Anne Macgregor-Das, Chiho Koi, Ki-Byung Song, Michael Borges, Ryo Sugimine, Daniel Laheru, Ralph H. Hruban, Nicholas Roberts, Alison P. Klein, Michael Goggins
Summary: Rare variants in CPB1 and CPA1 that induce endoplasmic reticulum (ER) stress are associated with increased odds of developing pancreatic cancer. Meta-analysis showed strong associations for both CPA1 and CPB1 ER-stress inducing variants with pancreatic cancer risk.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Gehan Botrus, Richard M. Miller, Pedro Luiz Serrano Uson Jr, Geoffrey Kannan, Haiyong Han, Daniel D. Von Hoff
Summary: High levels of ER stress and UPR activation are present in pancreatic cancer, leading to adaptive mechanisms and potential apoptosis. This review discusses the mechanisms by which compounds activate the UPR pathways and induce apoptosis, and explores the potential of ER stress inducers for anti-tumor efficacy in pancreatic cancer. A new approach of increasing ER stress and UPR activation to incite apoptotic cell death in pancreatic cancer is hypothesized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yanjuan Huang, Zilin Guan, Lingling Ren, Yong Luo, Meixu Chen, Yue Sun, Yuanfeng He, Zishan Zeng, Xiuling Dai, Jingwen Jiang, Zeqian Huang, Chunshun Zhao
Summary: We have engineered a pH-responsive nanoreactor that can self-supply Fenton catalysts and H2O2 within tumors, enabling tumor-specific chemo/chemodynamic therapy. The nanoreactor exhibits superior stability and activity, inducing oxidative stress and endoplasmic reticulum stress while repolarizing macrophages, providing a promising strategy for excellent cancer therapy.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Jian Yang, Huanji Xu, Wanlong Wu, Huixi Huang, Chenliang Zhang, Weiping Tang, Qinlin Tang, Feng Bi
Summary: Dysfunction of the ubiquitin-proteasome system can lead to sustained endoplasmic reticulum stress and cell death. Malignant cells have developed mechanisms to evade this stress. Understanding these mechanisms is important for exploiting drug-resistant tumors.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Chunmei Wen, Qingqing Ruan, Zhaofeng Li, Xiang Zhou, Xuezhi Yang, Pingwei Xu, Percy David Papa Akuetteh, Zheng Xu, Jie Deng
Summary: This study found that Cory inhibited the proliferation of pancreatic cancer cells, induced apoptosis, and promoted cell death by generating intracellular reactive oxygen species (ROS) and activating the p38 signaling pathway. Cory also exerted an anti-tumor effect by inducing endoplasmic reticulum stress.
BRITISH JOURNAL OF CANCER
(2022)
Review
Oncology
Faustino Mollinedo, Consuelo Gajate
Summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas with a dismal prognosis and survival rate. Novel therapeutic targets and drugs are urgently needed due to poor response of PDAC to current therapies. Direct targeting of the endoplasmic reticulum may be a promising approach in the therapy of pancreatic cancer.
Article
Biochemistry & Molecular Biology
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Kyu Chang Won
Summary: Brief Summary: The study demonstrates that pioglitazone selectively protects beta cells against high glucose-induced dysfunction by activating the AMPK and GLS1 axis, resulting in elevated GSH/GSSG ratio and inhibition of mitochondrial dysfunction.
Article
Oncology
Mariola Gimla, Agnieszka Pyrczak-Felczykowska, Marcelina Malinowska, Aleksandra Hac, Magdalena Narajczyk, Irena Bylinska, Tristan A. Reekie, Anna Herman-Antosiewicz
Summary: UA derivative 5 shows superior activity in inhibiting the growth and proliferation of pancreatic cancer cells. It induces ER stress and calcium ion release, leading to cell vacuolization. In a xenograft model, it effectively suppresses tumor growth without causing toxicity to the kidneys or liver.
CANCER CELL INTERNATIONAL
(2023)
Article
Chemistry, Physical
Junzong Chen, Miaojuan Qiu, Shiqiang Zhang, Binbin Li, Dong Li, Xiuyu Huang, Zhirong Qian, Jing Zhao, Zhiyong Wang, Di Tang
Summary: In this study, amino-capped polyamidoamine dendrimer was used as a macromolecular template to form amino-modified calcium phosphate hollow sphere for drug delivery application. The system loaded with 5-fluorouracil performed synergistic cancer chemotherapy by inducing calcium overload and reactive oxygen species accumulation in cancer cells, leading to apoptosis. The delivery system showed high tumor inhibition via chemotherapy with minimal impact on normal cells and organs, demonstrating good biocompatibility.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Narathip Naradun, Krajang Talabnin, Kanyavee Issarangkul Na Ayuttha, Chutima Talabnin
Summary: Cholangiocarcinoma is a lethal malignancy with limited treatment options. Piperlongumine, a biologically active alkaloid, has shown potential as a therapeutic option for cholangiocarcinoma by inducing cancer cell death. Combination treatment with piperlongumine and a proteasome inhibitor further enhances the anti-cancer activity. This research provides valuable insights into the potential use of piperlongumine as an alternative therapy for cholangiocarcinoma.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Balamurugan Dhayalan, Michael D. Glidden, Alexander N. Zaykov, Yen-Shan Chen, Yanwu Yang, Nelson B. Phillips, Faramarz Ismail-Beigi, Mark A. Jarosinski, Richard D. DiMarchi, Michael A. Weiss
Summary: The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin's biosynthetic precursor. This study used a peptide model to investigate representative clinical mutations and found striking correlations between peptide properties, ER stress, and age of diabetes onset.
FRONTIERS IN ENDOCRINOLOGY
(2022)