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Hydroxychloroquine (HCQ) disrupts both collective and individual cell migration by interfering with actin and vimentin cytoskeletal dynamics, as demonstrated in scratch assay experiments with HeLa cells. The drug binds cooperatively to actin with micromolar affinity, reducing filament polymerisation rates, decreasing actin density at wound edges, and impairing interactions with actin-binding proteins. Additionally, HCQ softens the cytoplasm, reorganizes the vimentin network, and suppresses lamellipodial protrusive activity, collectively compromising the mechanical and structural basis of directed cell migration.
Why it matters
These findings suggest that HCQ's ability to restrict cytoskeletal dynamics and cellular invasive capacity may have therapeutic relevance in oncology, potentially limiting tumour cell migration and progression. If validated in more complex biological models, this could support repurposing of an already clinically approved drug as an anticancer agent.
⚠️ Preprint – Noch nicht peer-reviewed
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Hydroxychloroquine (HCQ), a clinically relevant quinoline derivative, impairs both collective and individual cell migration by disrupting actin and vimentin cytoskeletal dynamics during wound healing. In scratch assays with HeLa cells, HCQ treatment significantly reduces wound closure rates and inhibits bursts of coordinated migration, as well as single-cell motility. Quantitative imaging reveals that HCQ diminishes actin filament density at the wound edge and induces reorganization of the vimentin network, resulting in smaller nuclei and compromised structural connectivity. Particle tracking micro-rheology demonstrates that HCQ softens the cytoplasm and decreases cellular mechanical heterogeneity. In vitro spectroscopic studies show that HCQ binds cooperatively to actin with micromolar affinity, perturbing its secondary structure, reducing filament polymerisation rates, and impairs interactions between actin and actin binding proteins (ABPs). HCQ also significantly suppresses lamellipodial protrusive activity, indicating a link between cytoskeletal remodelling and impaired cell migration. Collectively, these findings establish that HCQ disrupts essential mechanisms for directed migration by modulating the cytoskeleton and cell mechanics. This multifaceted impairment may underlie therapeutic potential of HCQ as an anticancer agent by restricting cellular invasive capacity and remodelling required for tumour progression.
Source: Hydroxychloroquine alters the cytoskeleton to impair cell migration