Article
Biochemistry & Molecular Biology
Yujeong Lee, Yoshiyuki Onishi, Lisa McPherson, Anna M. Kietrys, Marian Hebenbrock, Yong Woong Jun, Ishani Das, Shanthi Adimoolam, Debin Ji, Michael G. Mohsen, James M. Ford, Eric T. Kool
Summary: Impaired DNA repair activity is associated with increased cancer rates. This study found that certain tyrosine kinase inhibitors, such as nilotinib, can activate the repair enzyme MTH1, which cleanses oxidatively damaged nucleotides. Structural optimization resulted in compounds that strongly activate MTH1 and decrease mutagenic nucleotides in cellular DNA. These findings suggest that MTH1 activators may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Chang Min Lee, Jongsung Lee, Mi-Ae Kang, Hee Taek Kim, Jongbok Lee, Kyungmoon Park, Yung-Hun Yang, Kyu Yun Jang, See-Hyoung Park
Summary: Linifanib has been shown to efficiently inhibit receptor tyrosine kinases, and in this study, its anti-cancer effects in ovarian cancer were investigated. Linifanib was found to inhibit proliferation and induce apoptosis in SKOV3 cells, as well as cause DNA damage and increase intracellular ROS levels.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Oncology
Mohd Farhan, Asim Rizvi, Ferasat Ali, Aamir Ahmad, Mohammad Aatif, Arshi Malik, Mir Waqas Alam, Ghazala Muteeb, Saheem Ahmad, Awal Noor, Farhan Asif Siddiqui
Summary: Anthocyanidins can induce DNA damage and inhibit cell proliferation in cancer cells by reacting with intracellular copper. Copper supplementation increases the sensitivity of normal cells to anthocyanidins and decreases cell proliferation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Robert B. Rosenblatt, Joseph A. Frank, Scott R. Burks
Summary: The study found that non-ablative pulsed focused ultrasound (pFUS) directly induces DNA damage in various tumor cell types by triggering superoxide and subsequent H2O2 formation through cytosolic calcium transients. These results support the potential clinical utility of pFUS.
Review
Biochemistry & Molecular Biology
Fan Yang, Zhigang Hu, Zhigang Guo
Summary: DNA damage repair is crucial for maintaining genomic stability and integrity, and FEN1 plays a critical role in this process. Abnormal expression or mutation of FEN1 is associated with various diseases, including cancers, making it a therapeutic target for cancer treatment. Small-molecule compounds targeting FEN1 have been developed and show promise in cancer therapy.
Review
Chemistry, Medicinal
Junmin Zhang, Dongzhu Duan, Zi-Long Song, Tianyu Liu, Yanan Hou, Jianguo Fang
Summary: Regulating intracellular ROS levels may be an effective strategy for cancer prevention or treatment. This can be achieved through chemoprevention to reduce ROS production pathways, or through ROS-mediated anticancer therapy to stimulate ROS clearance, ultimately inhibiting tumor growth.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Senzhen Wang, Xiaojuan Xu, Delu Che, Ronghui Fan, Mengke Gao, Yue Cao, Chaochao Ge, Yongli Feng, Jinghua Li, Songqiang Xie, Chaojie Wang, Fujun Dai, Lei Gao, Yuxia Wang
Summary: The study confirmed that mitochondria are the main source of ROS induced by 6c, leading to mitochondrial dysfunction and lysosomal destabilization. Moreover, ROS regulated the expression of 6c-mediated proteins, promoted the formation of autophagosomes, and caused DNA damage, ultimately resulting in cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ankita Ray, Cristiana Passiu, Masayuki Nasuda, Shivaprakash N. Ramakrishna, Antonella Rossi, Akinori Kuzuya, Nicholas D. Spencer, Yoko Yamakoshi
Summary: A novel tripod molecule incorporating a C-60 photocatalyst was designed and immobilized onto an AFM tip for single-molecule level oxidative damage of DNA origami. The localized and temporally controlled oxidation of DNA origami was successfully achieved through singlet-oxygen generation from immobilized C-60 on the AFM tip under visible-light irradiation. This method allows for manipulation of various species on surfaces via controlled oxidation reactions triggered by locally generated singlet-oxygen from C-60 on the AFM tip.
Article
Medicine, Research & Experimental
Shan Zhang, Yue Zhao, Xueqi Wang, Ce Qi, Jialiang Tian, Zhihua Zou
Summary: In this study, we investigated the synergistic anticancer effect between ATR inhibition and oxidative DNA damage induced by the thioredoxin reductase inhibitor auranofin. Our findings suggest that auranofin can induce oxidative DNA damage selectively in cancer cells by increasing reactive oxygen species (ROS) levels, which leads to activation of the ATR DNA damage response pathway. Inhibition of ATR in auranofin-treated cancer cells results in replication catastrophe and potent synergistic lethality.
Article
Biochemistry & Molecular Biology
Birandra K. Sinha, Erik J. Tokar, Carl D. Bortner
Summary: NCX4040 exhibits cytotoxicity against ovarian tumor cells and induces apoptosis and oxidative stress. Sensitivity to NCX4040 and DNA damage repair efficiency vary among different cell lines, and the cytotoxicity may be mediated by peroxynitrite.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Kuiyang Zuo, Qi Xu, Yujie Wang, Yutong Sui, Ye Niu, Zinan Liu, Mingsheng Liu, Xinpeng Liu, Dan Liu, Wei Sun, Ziyu Wang, Xiaomei Liu, Jinyu Liu
Summary: Methylmercury (MeHg) is a toxic substance that causes oxidative damage to neurons. Vitamin C, a well-known antioxidant, can protect neurons from oxidative damage. In this study, we found that supplementation with L-ascorbic acid 2-phosphate (AA2P) could attenuate MeHg-induced apoptosis by reducing reactive oxygen species (ROS)-mediated DNA damage. AA2P also increased cell viability and decreased MeHg-induced apoptosis. Furthermore, it regulated gene expression in a contrary manner compared to MeHg. This study suggests that AA2P may be a potential treatment for MeHg neurotoxicity.
Review
Pharmacology & Pharmacy
Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Summary: Immunotherapy has revolutionized cancer treatment, with current therapies mostly based on antibodies. However, these therapies have limitations in terms of pharmacokinetics and immunogenicity. To overcome these limitations, researchers have focused on developing small molecule-based immunotherapy. This review provides an overview of the progress in small molecule-based immunomodulators for cancer therapy, including targeting PD-1/PD-L1, chemokine receptors, STING, TLR, etc. The importance of combining small molecule-based immunomodulators with therapeutic antibodies is also highlighted.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Plant Sciences
Dandan Huang, Guangqin Jing, Lili Zhang, Changbao Chen, Shuhua Zhu
Summary: NO, H2S, and ROS play essential signaling roles in cells through oxidative post-translational modification within suitable ranges of concentration to maintain redox balance and regulate DNA repair pathways, including mtDNA. The interactions among them are intricate, influencing their generation, elimination, and signaling actions. Additionally, NO and H2S may be involved in epigenetic variations in DNA damage repair of plants.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Mengying He, Mengyuan Wang, Tao Xu, Mengyao Zhang, Huaxing Dai, Chao Wang, Dawei Ding, Zhiyuan Zhong
Summary: Reactive oxygen species (ROS) act as important signaling molecules that can stimulate the immune system. ROS has emerged as a unique therapeutic strategy for malignant tumors because it can directly reduce tumor burden and induce immunogenic cell death (ICD) to trigger immune responses. However, immunosuppressive signals and dysfunction of immune cells within the tumor microenvironment (TME) often downplay the anti-tumor immune responses. Various strategies have been developed to enhance ROS-based cancer immunotherapy, such as combining with immune checkpoint inhibitors, tumor vaccines, and immunoadjuvants, which have shown promising results with limited side effects. This review introduces the concept of ROS-powered cancer immunotherapy, highlights innovative strategies to boost ROS-based cancer immunotherapy, and discusses challenges in clinical translation and future perspectives.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Cheng Peng, Yu-Hsuan Li, Chao-Wu Yu, Ze-Hua Cheng, Jia-Rong Liu, Jui-Ling Hsu, Ling-Wei Hsin, Chen-Tsung Huang, Hsueh-Fen Juan, Ji-Wang Chern, Yi-Sheng Cheng
Summary: MTH1 is a key enzyme that plays a role in DNA repair, preventing the insertion of incorrect nucleotides and reducing cell apoptosis caused by DNA damage. Through screening for lead compounds, several compounds with MTH1 inhibitory activity were identified, with MI0639 showing the highest effective inhibition. Compound derivatives were synthesized to explore the selectivity and specificity of the action, leading to the discovery of two compounds, MI1020 and MI1024, with nanomolar-range IC50 inhibition abilities.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ioannis Karakasiliotis, Nefeli Lagopati, Konstantinos Evangelou, Vassilis G. Gorgoulis
Summary: In-depth analysis of SARS-CoV-2 biology and pathogenesis has revealed the mechanisms through which the virus induces COVID-19 pathology. Cellular senescence, linked to SARS-CoV-2 infection, may contribute to virus mutagenesis through the action of RNA-editing enzymes like APOBEC. Understanding this mechanism of virus evolution highlights the importance of inhibiting cellular senescence in SARS-CoV-2 clinical treatment.
Article
Chemistry, Medicinal
Olov Wallner, Armando Cazares-Korner, Emma Rose Scaletti, Geoffrey Masuyer, Tove Bekkhus, Torkild Visnes, Kirill Mamonov, Florian Ortis, Thomas Lundback, Maria Volkova, Tobias Koolmeister, Elisee Wiita, Olga Loseva, Monica Pandey, Evert Homan, Carlos Benitez-Buelga, Jonathan Davies, Martin Scobie, Ulrika Warpman Berglund, Christina Kalderen, Pal Stenmark, Thomas Helleday, Maurice Michel
Summary: 8-oxo Guanine DNA Glycosylase 1 is the key enzyme in base excision repair, playing a critical role in the removal of oxidized guanines from damaged DNA. The optimization campaign resulted in the development of TH5487, a widely used tool compound for targeting OGG1. X-ray crystallography revealed the surprising binding mode of TH8535, the most potent member of a class of N-piperidinyl-benzimidazolones, which adopts a chair conformation rather than a boat conformation. Cellular studies demonstrated the target engagement and efficacy of TH8535 against various cancer cell lines.
Article
Pharmacology & Pharmacy
Marie-Noeurolle Paludetto, Mika Kurkela, Helina Kahma, Janne T. Backman, Mikko Niemi, Anne M. Filppula
Summary: This study aimed to explore the cytochrome P450 metabolic and inhibitory profile of hydroxychloroquine (HCQ). The results showed that CYP3A4, CYP2D6, and CYP2C8 are the key enzymes involved in HCQ metabolism. HCQ and its metabolites showed reversible inhibition of CYP2D6 and time-dependent inhibition of CYP3A. Rating: 8/10.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Biochemical Research Methods
Zeljka Popovic, Lissa C. Anderson, Xuepei Zhang, David S. Butcher, Greg T. Blakney, Roman A. Zubarev, Alan G. Marshall
Summary: Isotopic depletion of growth medium improves protein mass measurement accuracy and signal-to-noise ratio, enabling better mass spectrometry analysis for both bacteria and eukaryotes.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Pharmacology & Pharmacy
Minna Lehtisalo, Wilma Kiander, Anne M. M. Filppula, Feng Deng, Heidi Kidron, Mari Korhonen, Johanna Sinkko, Kimmo Koivula, Mikko Niemi
Summary: We report 3 cases of rhabdomyolysis diagnosed in patients 1-6 months after the concurrent use of rosuvastatin and ticagrelor. A review of the literature and the Food and Drug Administration adverse event reporting system revealed more than 40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 fatal cases. In vitro studies showed that ticagrelor inhibits the transport of rosuvastatin by breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1, with inhibitory concentrations ranging from 0.36 to 7.5 μM. Our findings suggest that the concomitant use of ticagrelor and rosuvastatin may lead to an increased risk of rosuvastatin-induced rhabdomyolysis due to the inhibition of rosuvastatin transport. Further research is needed to investigate the pharmacokinetic interaction between ticagrelor and rosuvastatin in humans.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nils Kurzawa, Isabelle Rose Leo, Matthias Stahl, Elena Kunold, Isabelle Becher, Anastasia Audrey, Georgios Mermelekas, Wolfgang Huber, Andre Mateus, Mikhail M. Savitski, Rozbeh Jafari
Summary: Using thermal proteome profiling, we detected 15,846 proteoforms expressed from 9,290 genes in acute lymphoblastic leukemia cell lines. We identified differential co-aggregation of proteoform pairs and their links to disease biology. Furthermore, we used measured biophysical proteoform states to find specific biomarkers of drug sensitivity, providing a powerful tool for systematic detection and functional annotation of proteoform groups.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Gustav Christensen, Yiyi Chen, Dileep Urimi, Laimdota Zizmare, Christoph Trautwein, Nicolaas Schipper, Francois Paquet-Durand
Summary: Despite the shortage of drug treatments for retinal diseases, transporter-targeted liposomes coated with substrates for highly expressed transporter proteins have shown promise for targeted drug delivery to photoreceptors. In this study, we identified the MCT transporter as a potential target and evaluated its suitability for drug delivery using different monocarboxylate-conjugated liposomes. Pyruvate-conjugated liposomes displayed the highest cell uptake, and pharmacological inhibition of MCT reduced internalization, suggesting an MCT-dependent uptake mechanism. Notably, pyruvate-conjugated liposomes loaded with the drug candidate CN04 effectively reduced photoreceptor cell death in a retinal degeneration model. This study highlights the potential of pyruvate-conjugated liposomes for targeted drug delivery to retinal photoreceptors and other neurons with high expression of MCT-type proteins.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Minna Lehtisalo, E. Katriina Tarkiainen, Mikko Neuvonen, Mikko Holmberg, Johanna I. Kiiski, Outi Lapatto-Reiniluoto, Anne M. Filppula, Mika Kurkela, Janne T. Backman, Mikko Niemi
Summary: Ticagrelor increases the plasma concentration of rosuvastatin in humans, most likely by inhibiting intestinal BCRP. Therefore, concurrent use of ticagrelor and high doses of rosuvastatin should be avoided.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemical Research Methods
Irina D. D. Vasileva, Tatiana Yu. Samgina, Zhaowei Meng, Roman A. A. Zubarev, Albert T. T. Lebedev
Summary: In traditional proteomic analysis, disulfide bonds in peptides pose a problem for sequencing, requiring multiple reaction steps. However, this study found that EThcD technology can sequence peptides with disulfide bonds without the need for chemical derivatization.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemistry & Molecular Biology
Tatiana Yu. Samgina, Irina D. Vasileva, Polonca Trebse, Gregor Torkar, Alexey K. Surin, Zhaowei Meng, Roman A. Zubarev, Albert T. Lebedev
Summary: Peptides released on frogs' skin in a stress situation are their only weapon against micro-organisms and predators. Each frog population has its own unique peptidome suitable for their habitat. This study analyzed the peptidome composition of the Central Slovenian agile frog population, and discovered multiple peptide families.
Article
Biochemistry & Molecular Biology
Amir Ata Saei, Hassan Gharibi, Hezheng Lyu, Brady Nilsson, Maryam Jafari, Hans Von Holst, Roman A. Zubarev
Summary: The study investigated the molecular consequences of traumatic brain injuries using a proteomics approach. It found that dynamic impacts led to reduced neuron viability and significant changes in protein solubility. The affected proteins were involved in various pathways, including cell adhesion, stress response, immune response, complement, and coagulation cascades.
Article
Biotechnology & Applied Microbiology
K. Ivar Lonnberg, Aleksi Tornio, Paivi Hirvensalo, Jenni Keskitalo, Anna-Liina Mustaniemi, Johanna I. Kiiski, Anne M. Filppula, Mikko Niemi
Summary: This study investigated the associations between SLCO1B1 c.521T>C and the intolerance to atorvastatin, fluvastatin, pravastatin, rosuvastatin, or simvastatin, between ABCG2 c.421C>A and the intolerance to atorvastatin, fluvastatin, or rosuvastatin, and between CYP2C9*2 and *3 alleles and the intolerance to fluvastatin. The results confirmed the association of SLCO1B1 c.521C/C genotype with simvastatin intolerance and suggested the feasibility for larger future studies.
PHARMACOGENETICS AND GENOMICS
(2023)
Article
Multidisciplinary Sciences
Shane C. Wright, Aikaterini Motso, Stefania Koutsilieri, Christian M. Beusch, Pierre Sabatier, Alessandro Berghella, Elodie Blondel-Tepaz, Kimberley Mangenot, Ioannis Pittarokoilis, Despoina-Christina Sismanoglou, Christian Le Gouill, Jesper V. Olsen, Roman A. Zubarev, Nevin A. Lambert, Alexander S. Hauser, Michel Bouvier, Volker M. Lauschke
Summary: This study investigates the subcellular location of GLP-1R signaling events and reveals associations between signaling profiles and adverse drug reactions, providing important insights for rational drug design and improving the therapeutic potential of GLP-1R agonists.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Zhongwei Xu, Bingze Xu, Susanna L. Lundstrom, Alex Moreno-Giro, Danxia Zhao, Myriam Martin, Erik Lonnblom, Qixing Li, Alexander Kramer, Changrong Ge, Lei Cheng, Bibo Liang, Dongmei Tong, Roma Stawikowska, Anna M. Blom, Gregg B. Fields, Roman A. Zubarev, Rikard Holmdahl
Summary: This study developed antibodies targeting type-II collagen and investigated their mechanism of action. The antibody R69-4 inhibits autoantibody-mediated arthritis by hindering FCGR3 signaling, highlighting its potential clinical utility in acute rheumatoid arthritis.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Bara A. Badwan, Gerry Liaropoulos, Efthymios Kyrodimos, Dimitrios Skaltsas, Aristotelis Tsirigos, Vassilis G. Gorgoulis
Summary: In recent years, there has been increasing interest in using machine learning algorithms (MLAs) in oncology for various biomedical applications. MLAs have the potential to provide valuable insights and predictions by representing both the disease state and therapeutic agents. This perspective paper lays out approaches to effectively utilize MLAs in oncology by representing both the disease state and therapeutic agents, leading to novel insights and relevant predictions.
CELL REPORTS METHODS
(2023)