Article
Chemistry, Multidisciplinary
Hieu T. M. Nguyen, Nitesh Katta, Jessica A. Widman, Eri Takematsu, Xu Feng, Susana A. Torres-Hurtado, Tania Betancourt, Aaron B. Baker, Laura J. Suggs, Thomas E. Milner, James W. Tunnell
Summary: This study found that using gold nanorods and laser irradiation can induce cancer cell death, increase the expression of damage-associated molecular patterns, and promote the activation of dendritic cells.
Article
Cell Biology
Zhe Liu, Liang Ma, Yiming Sun, Wenying Yu, Xue Wang
Summary: The study demonstrated that the STAT3/ZEB1 axis is critical in gefitinib resistance in lung cancer, and a new potential therapeutic strategy targeting STAT3 has been identified with the inhibitor LL1. LL1 was shown to sensitize resistant cells to gefitinib by depleting STAT3 activity and blocking its signaling pathways, with little observed toxicity in animal models, indicating it could be a chemotherapeutic adjuvant for gefitinib resistance in NSCLC.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Kento Kawasaki, Kazuhiro Noma, Takuya Kato, Toshiaki Ohara, Shunsuke Tanabe, Yasushige Takeda, Hijiri Matsumoto, Seitaro Nishimura, Tomoyoshi Kunitomo, Masaaki Akai, Teruki Kobayashi, Noriyuki Nishiwaki, Hajime Kashima, Naoaki Maeda, Satoru Kikuchi, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
Summary: The PD-1/PD-L1 axis plays a crucial role in tumor immunosuppression, and the mutual enhancement of PD-L1 expression between cancer cells and CAFs leads to tumor immunosuppression. PD-L1-expressing CAFs may be promising targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Chemistry, Multidisciplinary
Yannan Yang, Zhengying Gu, Jie Tang, Min Zhang, Yang Yang, Hao Song, Chengzhong Yu
Summary: The study challenges the traditional view of MnO2 nanoparticles as merely assisting in cancer immunotherapy, revealing their intrinsic immunomodulatory property in inducing immunogenic cell death. This unique property is exploited for a new cancer starvation-immunotherapy approach, showing promising efficacy in suppressing local and distant tumors.
Article
Plant Sciences
Yili Shen, Haijian Cai, Shenjie Ma, Wenjing Zhu, Haiyang Zhao, Jifa Li, Hua Ye, Lehe Yang, Chengguang Zhao, Xiaoying Huang, Zhongxiao Xiao
Summary: Telocinobufagin can inhibit proliferation and metastasis, and induce apoptosis in non-small-cell lung cancer cells. Its mechanism of action involves inhibition of STAT3 phosphorylation and downstream targets, as well as interference with IL-6-induced STAT3 nuclear translocation.
JOURNAL OF NATURAL PRODUCTS
(2022)
Review
Chemistry, Physical
Di Li, Siqi Liu, Yang Ma, Shixian Liu, Yahui Liu, Jianxun Ding
Summary: The immune system plays a vital role in the occurrence and development of cancer. Immunotherapy offers a promising approach to treat and cure cancer. During immunotherapy, the immunogenic cell death (ICD) of tumor cells activates innate and adaptive immune responses by releasing tumor-associated antigens and damage-associated molecular patterns. This review summarizes the progress in using biomaterials to induce ICD and discusses their potential application in cancer immunotherapy.
Article
Oncology
Amriti R. Lulla, Yan Zhou, Marie D. Ralff, Avital Lev, David T. Dicker, Wafik S. El-Deiry
Summary: TRAIL-based therapies are a promising approach for selectively killing cancer cells, but limited serum half-life hinders their clinical development. This study identifies a novel miRNA, miR-3132, which induces TRAIL and apoptosis in cancer cells via the interferon signaling pathway. This discovery provides new insights into the potential of miR-3132 as a therapeutic target for cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Kamilla Stahl-Meyer, Mesut Bilgin, Lya K. K. Holland, Jonathan Stahl-Meyer, Thomas Kirkegaard, Nikolaj Havnsoe Torp Petersen, Kenji Maeda, Marja Jaattela
Summary: GalSph and GlcSph are lysosome-destabilizing lipids that induce cell death in breast cancer cells and primary fibroblasts independently of lysosomal Ca2+ efflux, and through activation of the cAMP signaling pathway.
Article
Biotechnology & Applied Microbiology
Xiaoli Zhang, Yi Lu, Die Jia, Wei Qiu, Xianbin Ma, Xingliang Zhang, Zhigang Xu, Feiqiu Wen
Summary: The research developed an acidity-responsive polymeric metal organic framework nanoparticle (DIMP) for delivering doxorubicin and indocyanine green for breast carcinoma theranostics, demonstrating efficient tumor accumulation and immunogenic cell death effect, highlighting the potential of the strategy for synergistic tumor therapy.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xiaojuan Yang, Lu Xu, Li Yang, Shaohong Xu
Summary: STAT3 is a transcription factor that regulates gene levels associated with cell survival, cell cycle, and immune reaction. It is linked to malignancy and the development of various cancers, making targeting STAT3 protein a promising therapeutic strategy. However, the development of STAT3 inhibitors faces challenges such as toxic effects, limited therapeutic effects, and drug resistance.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Acharya Balkrishna, Vallabh Prakash Mulay, Sudeep Verma, Jyotish Srivastava, Savita Lochab, Anurag Varshney
Summary: The extract from Pistacia integerrima contains penta-O-galloyl-beta-D-glucose (PGG), which shows potential in inhibiting lung cancer progression by modulating the ERK/AMPK-ULK1/STAT3 signaling axis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Acharya Balkrishna, Vallabh Prakash Mulay, Sudeep Verma, Jyotish Srivastava, Savita Lochab, Anurag Varshney
Summary: The plant extract from Pistacia integerrima containing PGG effectively combats lung cancer progression through autophagic cell death by altering ERK/AMPK-ULK1/STAT3 signaling axes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Douglas Ribeiro Lucas, Filipe Zaniratti Damica, Estefany Braz Toledo, Antonio Jesus Dorighetto Cogo, Anna Lvovna Okorokova-Facanha, Valdirene Moreira Gomes, Andre de Oliveira Carvalho
Summary: The research findings suggest that the bioinspired peptides induced different death kinetics in Candida tropicalis and Candida albicans, with RR and WR causing non-accidental cell death and D-RR inducing programmed cell death metacaspase-independent. These results provide a better understanding of the death process induced by these peptides.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2023)
Article
Chemistry, Medicinal
Endri Karaj, Shaimaa H. Sindi, Nishanth Kuganesan, Lalith Perera, William Taylor, L. M. Viranga Tillekeratne
Summary: This article explores the renewed interest in covalent inhibitors in drug discovery and the discovery of a new class of tunable heterocyclic electrophiles capable of inducing ferroptosis. The results show that these heterocycles selectively induce ferroptosis with high potency. Further analysis suggests that these compounds can undergo thiol addition and their potential target is the GPX4 protein. Incorporation of these heterocycles into appropriate pharmacophores generates highly cytotoxic agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Pathum S. Thilakasiri, Rhynelle S. Dmello, Tracy L. Nero, Michael W. Parker, Matthias Ernst, Ashwini L. Chand
Summary: Drug repurposing is a valuable approach for rapidly introducing new cancer therapies into clinical practice. STAT3 inhibitors play a significant role in cancer treatment, but challenges remain in understanding the mechanisms of STAT3 activation and developing strategies to suppress its activity with various pharmaceutical agents.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Radosveta Gencheva, Elias S. J. Arner
Summary: Cytosolic selenoprotein thioredoxin reductase 1 (TrxR1) and mitochondrial TrxR2 (TXNRD2) can be inhibited by a wide range of electrophilic compounds, which may have important implications for cancer therapy.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Huidan Yu, Xueyan Song, Fan Yang, Jun Wang, Mingjian Sun, Guangxin Liu, Nafees Ahmad, Yuanshuai Zhou, Yina Zhang, Guohua Shi, Ruobing Zhang, Jianping Liu, Xiaobing Jiang, Peng Fu, Gang Chen, Jingmei Li, Jie Zhuang, Minxuan Sun
Summary: This study investigated the therapeutic combination of vitamin C and plasma-conditioned medium on glioblastoma cells in culture and in xenograft models. The combination treatment reduced cell viability and proliferation, while promoting apoptosis, with stronger effects than either treatment alone. Mechanistic insights were provided, suggesting the potential of this combination therapy against glioblastoma and other potential therapies.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Maria Schwarz, Alina Loeser, Qing Cheng, Mareike Wichmann-Costaganna, Patrick Schaedel, Oliver Werz, Elias S. J. Arner, Anna P. Kipp
Summary: In humans, there are eight glutathione peroxidases (GPXs), and five of them are selenoproteins that play a crucial role in cellular redox homeostasis. Among the three main cytosolic GPXs, GPX1 and GPX2 reduce soluble hydroperoxides, while GPX4 reduces complex lipid hydroperoxides. The experiments show that GPX1 has the highest activity in reducing soluble and fatty-acid derived hydroperoxides among these isoforms.
Article
Chemistry, Medicinal
Anniina T. Virtanen, Teemu Haikarainen, Parthasarathy Sampathkumar, Maaria Palmroth, Sanna Liukkonen, Jianping Liu, Natalia Nekhotiaeva, Stevan R. Hubbard, Olli Silvennoinen
Summary: This study identified novel small molecules targeting the JH2 domain of JAK2 V617F and characterized their binding properties. Screening of a large number of small molecules resulted in the identification of 55 binders to the ATP-binding pocket of JAK2 JH2 V617F protein. These findings reveal the unique structural characteristics of the JAK2 JH2 ATP-binding pocket.
Article
Biochemistry & Molecular Biology
Angelos Heldin, Matko Cancer, Mireia Palomar-Siles, Susanne Ohlin, Meiqiongzi Zhang, Alexander Sun-Zhang, Anna Mariani, Jianping Liu, Vladimir J. N. Bykov, Klas G. G. Wiman
Summary: The TP53 and PTEN tumour suppressor genes are frequently inactivated by nonsense mutations in human tumours. In this study, two novel compounds were identified that can induce translational readthrough and restore the expression of full-length p53 protein in cells with TP53 nonsense mutations. Compound C47 showed synergy with G418, a known readthrough inducer, while compound C61 synergized with eRF3 degraders CC-885 and CC-90009. Furthermore, compound C47 also demonstrated potent induction of full-length PTEN protein in cells with different PTEN nonsense mutations. These findings may have implications for the development of targeted cancer therapy by pharmacologically inducing translational readthrough.
Article
Biochemistry & Molecular Biology
Dorian M. Cheff, Chuying Huang, Karoline C. Scholzen, Radosveta Gencheva, Michael H. Ronzetti, Qing Cheng, Matthew D. Hall, Elias S. J. Arner
Summary: Ferroptosis refers to cell death triggered by iron-dependent lipid peroxidation, which can be prevented by antioxidant compounds like ferrostatin-1. Endogenous suppressors of ferroptosis include FSP-1 and the selenoprotein GPX4, while small molecules like RSL3 and ML162 can induce ferroptosis by inhibiting GPX4. However, our findings suggest that RSL3 and ML162 may not inhibit GPX4 enzymatic activity as previously believed, but instead function as inhibitors of another selenoprotein, TXNRD1. These results highlight the need for reevaluation of previous studies using RSL3 and ML162 in the context of ferroptosis.
Editorial Material
Medicine, General & Internal
Qian Xu, Jianping Liu
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Luana Naia, Makoto Shimozawa, Erika Bereczki, Xidan Li, Jianping Liu, Richeng Jiang, Romain Giraud, Nuno Santos Leal, Catarina Moreira Pinho, Erik Berger, Victoria Lim Falk, Giacomo Dentoni, Maria Ankarcrona, Per Nilsson
Summary: This study investigates the sequential onset of AD-like pathologies in App knock-in mice and reveals that energy metabolism is significantly altered at an early stage of pathology. As the pathology progresses, the brain shifts to a state of hypometabolism and synaptic abnormalities occur, including accumulation of synaptic vesicles and autophagosomes.
MOLECULAR PSYCHIATRY
(2023)
Article
Microbiology
Xinxian Wang, Junlong Bi, Chao Yang, Yongneng Li, Ying Yang, Junwen Deng, Lei Wang, Xiaolin Gao, Yingbo Lin, Jianping Liu, Gefen Yin
Summary: Porcine reproductive and respiratory syndrome (PRRS) is a significant swine disease with challenging control. This study revealed that PRRSV infection upregulated the expression of LOC103222771, which might be an upstream regulator of CLDN4. Downregulation of CLDN4 could enhance PRRSV infection. The LOC103222771/CLDN4 signal axis might be a novel mechanism of PRRSV pathogenesis.
VETERINARY MICROBIOLOGY
(2023)
Article
Virology
Xinxian Wang, Junlong Bi, Ying Yang, Lijun Li, Runting Zhang, Yongneng Li, Meiling Cheng, Wenying Li, Guishu Yang, Yingbo Lin, Jianping Liu, Gefen Yin
Summary: Porcine reproductive and respiratory syndrome (PRRS) is an acute infectious disease that poses a serious threat to the pig industry. This study found that downregulation of cellular RACK1 inhibited ERK1/2 activation and suppressed PRRSV infection, while overexpression of RACK1 enhanced ERK1/2 activation and PRRSV infection. Further analysis revealed that cellular RACK1 could interact with viral N protein to exert its function in promoting PRRSV replication.
Article
Biochemistry & Molecular Biology
Attila Andor, Mahendravarman Mohanraj, Zsuzsanna Anna Pato, Katalin Uri, Beata Biri-Kovacs, Qing Cheng, Elias S. J. Arner
Summary: TXNL1 has dual functions, acting as a supporting factor for TrxR1-driven redox activities in disulfide reduction reactions and functioning as an ATP-independent chaperone.
Article
Biochemistry & Molecular Biology
Dorian M. Cheff, Qing Cheng, Hui Guo, Jameson Travers, Carleen Klumpp-Thomas, Min Shen, Elias S. J. Arner, Matthew D. Hall
Summary: Selenoprotein glutathione peroxidases (GPX) have antioxidant activities by reducing hydroperoxides using glutathione. Overexpression of GPXs is common in cancer and associated with chemotherapy resistance. Inhibitors of GPX1 and GPX4 have potential as anti-cancer agents, and targeting other GPX isoforms may be beneficial. The development of direct GPX inhibitors through screening could be valuable.
Meeting Abstract
Ophthalmology
Xiaoyuan Ren, Arne Holmgren, Elias S. J. Arner, Thierry D. Leveillard
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Oncology
Igor Govorov, Sanaz Attarha, Larysa Kovalevska, Emil Andersson, Elena Kashuba, Miriam Mints
Summary: This study found that the expression of PKN1 is associated with the prognosis of endometrial cancer patients, and it may serve as a candidate prognostic marker for EC.
Article
Oncology
Nadilly Bonagas, Nina M. S. Gustafsson, Martin Henriksson, Petra Marttila, Robert Gustafsson, Elisee Wiita, Sanjay Borhade, Alanna C. Green, Karl S. A. Vallin, Antonio Sarno, Richard Svensson, Camilla Gokturk, Therese Pham, Ann-Sofie Jemth, Olga Loseva, Victoria Cookson, Nicole Kiweler, Lars Sandberg, Azita Rasti, Judith E. Unterlass, Martin Haraldsson, Yasmin Andersson, Emma R. Scaletti, Christoffer Bengtsson, Cynthia B. J. Paulin, Kumar Sanjiv, Eldar Abdurakhmanov, Linda Pudelko, Ben Kunz, Matthieu Desroses, Petar Iliev, Katarina Farnegardh, Andreas Kramer, Neeraj Garg, Maurice Michel, Sara Haggblad, Malin Jarvius, Christina Kalderen, Amanda Bogedahl Jensen, Ingrid Almlof, Stella Karsten, Si Min Zhang, Maria Haggblad, Anders Eriksson, Jianping Liu, Bjorn Glinghammar, Natalia Nekhotiaeva, Fredrik Klingegard, Tobias Koolmeister, Ulf Martens, Sabin Llona-Minguez, Ruth Moulson, Helena Nordstrom, Vendela Parrow, Leif Dahllund, Birger Sjoberg, Irene L. Vargas, Duy Duc Vo, Johan Wannberg, Stefan Knapp, Hans E. Krokan, Per Arvidsson, Martin Scobie, Johannes Meiser, Pal Stenmark, Ulrika Warpman Berglund, Evert J. Homan, Thomas Helleday
Summary: This study investigates the role of MTHFD2 in cancer cells and the effects of its inhibitors. The results demonstrate that MTHFD2 inhibitors can decrease DNA replication speed, induce replication stress, and ultimately lead to apoptosis in cancer cells. These findings reveal the functional link between MTHFD2-dependent cancer metabolism and replication stress, providing a potential therapeutic strategy.