Biology subjects

Bisoi, A.

Publications and source records attributed to Bisoi, A..

3 recordsLinked to original sources

bioRxiv2026

Hydroxychloroquine alters the cytoskeleton to impair cell migration

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.

cell biology↗

bioRxiv2025

Chemical Environment of the Confinement Governs Thermal Stability of the Folded Telomere G-Quadruplex

In this study, the effect of the chemical nature of the confinement on the folding and thermal stability of the telomere G-quadruplex (G4) has been investigated by studying the folding pattern of different telomere DNA sequences with varying numbers and arrangements of thymine loop nucleobases in the presence of anionic and cationic nanosized water pools. The findings suggest that both anionic and cationic water pools fold the telomere sequences into G4 of the same topology. However, the thermal stability of the folded G4 in the cationic water pool is significantly lower than that of the anionic case. The overall data indicate that the topology of the folded G4 is insensitive to the nature of the confinement, however, the thermal stability of the folded telomeric G4 depends significantly on the chemical nature of the confinement. It is plausible that the interfacial water inside the cationic water pools has a different orientation and hydrogen bonding than the case of anionic water pools, which may cause the different thermal stability of the G4 on these two water pools. These findings may be important in understanding the folding and stability of telomere G4 inside the confined cellular system.

biochemistry↗

bioRxiv2024

G-Quadruplex Mediated c-myc Specific Downregulation: A Unique Pathway of the Anticancer Action of Immunomodulator Drugs

AbstractHydroxychloroquine (HCQ), and chloroquine (CQ) are in the preclinical trial stage for cancer along with their active application in autoimmune diseases and malaria. One of the critical hallmarks of cancer cells is the elevated expression of various oncogenes which promote cancer progression and contribute to poor prognosis. The upstream of the promoter region of these oncogenes often exhibits a G-quadruplex (G4) DNA structure which regulates the gene expression. Hence, targeting G4 structure has emerged as a promising therapeutic strategy for cancer. In this study, the recognition of HCQ and CQ with the G4 structure of different oncogenes and its effect on gene regulation has been explored by a combination of various biophysical and in-vitro and in-vivo biological methods. This study depicts that HCQ and CQ downregulate the c-myc oncogene transcription significantly in a G4-dependent manner compared to other oncogenes. The different biophysical techniques and molecular dynamics simulation studies illustrate that these drug molecules stack predominately at the terminal of the c-myc G4 and the binding of these molecules stabilizes c-myc G4 significantly higher than the G4 structure of other oncogenes. The in-vitro cell data exhibit a notable reduction in both c-myc mRNA and protein levels in a triple-negative breast cancer cell line following HCQ treatment. The pre-clinical breast cancer mouse model in-vivo data also indicate that HCQ reduces tumor growth through the downregulation of the c-myc oncogene. Simultaneously, HCQ also enhances the therapeutic efficacy of standard chemotherapeutic agents to be a potential candidate for combination therapy. This work demonstrates the alternative strategy of anticancer action of widely used drugs by specifically downregulating the c-myc oncogene in a G4-dependent manner.

biochemistry↗