ArticleJournal of experimental & clinical cancer research : CR2022
Targeting selenoprotein H in the nucleolus suppresses tumors and metastases by Isovalerylspiramycin I.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Integrative Analysis of Gene and Protein Expression Data Reveals Novel Clusters for Ovarian Cancer Prognosis.International journal of molecular sciences · 2026Article
- [Using activity-based protein profiling method to explore the antitumor targets of spiramycin derivatives].Se pu = Chinese journal of chromatography · 2026Article
- Nutritional supplementation remodels yak cardiac molecular networks through selenoprotein activation and immune quiescence.Frontiers in nutrition · 2026Article
- Integrin CD103 expression in naive CD8Immunity · 2025Article
- Uncovering Anticancer Mechanisms of Spiramycin Derivatives Using Transcriptomic and Metabolomic Analyses.Metabolites · 2025Article
- Efficacy of carrimycin againstMicrobiology spectrum · 2025Article
- The synergistic antitumour effect of Carrimycin combined with 5-fluorouracil on colorectal cancer.Scientific reports · 2025Article
- Isovalerylspiramycin I alleviates liver injury and liver fibrosis by targeting the nucleotide-binding protein 2 (NUBP2)-vascular non-inflammatory molecule-1 (VNN1) pathway.Journal of pharmaceutical analysis · 2025Article
- Isovalerylspiramycin I Reprograms the Immunosuppressive and Temozolomide-Resistant Microenvironment by Inhibiting the Frizzled-5/Wnt/β-Catenin Pathway in Glioblastoma.Research (Washington, D.C.) · 2025Article
- Synthesis, anticancer and antibacterial evaluation of novel spiramycin-acylated derivatives.RSC advances · 2024Article
- The Art of Finding the Right Drug Target: Emerging Methods and Strategies.Pharmacological reviews · 2024Review
- Study of Bitespiramycin Distribution in Rats and Cerebrospinal Fluid of Patients by a Sensitive LC-MS/MS Method with Rapid Sample Preparation.Molecules (Basel, Switzerland) · 2024Article
- Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report.World journal of clinical cases · 2024Article
- Carrimycin in a Patient with Acute Myeloid Leukemia Complicated with Life-Threatening Mixed Perianal Infection: A Case Report and Literature Review.Infection and drug resistance · 2024Article
- Effects of selenoprotein extracts fromFrontiers in immunology · 2024Article
- The semisynthesis of nucleolar human selenoprotein H.Chemical science · 2023Article
- Carrimycin, a first in-class anti-cancer agent, targets selenoprotein H to induce nucleolar oxidative stress and inhibit ribosome biogenesis.Cancer pathogenesis and therapy · 2023Article
- Commentary to "Carrimycin, a first in-class anti-cancer agent, targets selenoprotein H to induce nucleolar oxidative stress and inhibit ribosomal biogenesis"☆.Cancer pathogenesis and therapy · 2023Article
- A Case of Multidrug-ResistantInfection and drug resistance · 2023Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCompared to normal cells, cancer cells exhibit a higher level of oxidative stress, which primes key cellular and metabolic pathways and thereby increases their resilience under oxidative stress. This higher level of oxidative stress also can be exploited to kill tumor cells while leaving normal cells intact. In this study we have found that isovalerylspiramycin I (ISP I), a novel macrolide antibiotic, suppresses cancer cell growth and tumor metastases by targeting the nucleolar protein selenoprotein H (SELH), which plays critical roles in keeping redox homeostasis and genome stability in cancer cells.
methodsWe developed ISP I through genetic recombination and tested the antitumor effects using primary and metastatic cancer models. The drug target was identified using the drug affinity responsive target stability (DARTS) and mass spectrum assays. The effects of ISP I were assessed for reactive oxygen species (ROS) generation, DNA damage, R-loop formation and its impact on the JNK2/TIF-IA/RNA polymerase I (POLI) transcription pathway.
resultsISP I suppresses cancer cell growth and tumor metastases by targeting SELH. Suppression of SELH induces accumulation of ROS and cancer cell-specific genomic instability. The accumulation of ROS in the nucleolus triggers nucleolar stress and blocks ribosomal RNA transcription via the JNK2/TIF-IA/POLI pathway, causing cell cycle arrest and apoptosis in cancer cells.
conclusionsWe demonstrated that ISP I links cancer cell vulnerability to oxidative stress and RNA biogenesis by targeting SELH. This suggests a potential new cancer treatment paradigm, in which the primary therapeutic agent has minimal side-effects and hence may be useful for long-term cancer chemoprevention.
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Registered trials
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