NQO1‐Responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell‐Targeted Migrastatic
Source abstract
Abstract
Abstract Migrastatic drugs targeting cell motility and suppressing invasiveness of solid tumors, have the potential to bring about a paradigm shift in the treatment of solid cancer. Cytochalasin B ( CB ) is a potent migrastatic compound, but its clinical use is limited by poor selectivity. Here, a NQO1‐responsive prodrug, BQTML‐CB is developed, synthesized in three steps from cytochalasin B derived from Preussia similis G22. BQTML‐CB is selectively activated in NQO1‐positive cancer cells, releasing active CB . In vitro , BQTML‐CB significantly inhibits proliferation and migration in NQO1‐positive U‐2OS cells, causing actin disruption and cytokinesis abnormalities, while sparing NQO1‐negative B16‐F1 cells. The prodrug shows reduced effects on human neutrophils, indicating reduced immunosuppressive activity of BQTML‐CB compared to CB . Co‐culture studies reveal a beneficial bystander effect, as cleaved CB diffused into adjacent NQO1‐deficient cells. These findings support BQTML‐CB as a cancer‐targeted prodrug with selective antiproliferative and migrastatic properties, highlighting the potential of C7‐OH‐modified cytochalasans in cancer therapy.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Microtubule and mitosis dynamics · Nanoplatforms for cancer theranostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry and Molecular Biology Division of Organic and Medicinal Chemistry University of Gothenburg Natrium, Medicinaregatan 7B Gothenburg 413 90 Sweden
Department of Cell Biology Helmholtz Centre for Infection Research Inhoffenstrasse 7 38124 Braunschweig Germany
Division of Molecular Cell Biology Zoological Institute Technische Universität Braunschweig Spielmannstrasse 7 38106 Braunschweig Germany
Department of Microbial Drugs Helmholtz Centre for Infection Research Inhoffenstrasse 7 38124 Braunschweig Germany
Department of Life Sciences Chalmers University of Technology Kemivägen 4 Göteborg 41296 Sweden
Department of Oral Microbiology and Immunology Institute of Odontology Sahlgrenska Academy University of Gothenburg Medicinaregatan 12F Göteborg 413 90 Sweden
Institute for Microbiology Technische Universität Braunschweig Spielmannstraße 7 38106 Braunschweig Germany
Funding
Stiftelsen Konung Gustaf V:s 80-årsfond · Vetenskapsrådet · Deutsche Forschungsgemeinschaft · Göteborgs Universitet
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