Poly-guanidine shows high cytotoxicity in glioma cell cultures and glioma stem cells.
Marcela Márquez-MéndezKarl Holmberg OlaussonAyodele AlaiyaSten NilssonLennart MeurlingAnders R HolmbergPublished in: Investigational new drugs (2022)
Glioblastoma multiforme (GBM) is a malignant CNS tumor with a poor prognosis. GBM shows aberrant glycosylation with hypersialylation. This property is a potential target for therapy. This study investigates the growth inhibitory efficacy of poly-guanidine (GuaDex), with an affinity for sialic acid (Sia). Glioma cell cultures and patient-derived glioma cell lines (PDGCLs) expressing Prominin-1 (CD133) were used. Human fibroblasts and astrocyte-derived cells were used as controls. Temozolomide (standard GBM drug, TMZ) and DMSO were used as a comparison. GuaDex at 1-10 µM concentrations, were incubated for 3.5-72 h and with PDGCLs cells for 6-24 h. The cytotoxicity was estimated with a fluorometric cytotoxicity assay (FMCA). Fluorescence-labelled GuaDex was used to study the cell interactions. Sia expression was confirmed with a fluorescence labelled Sia binding lectin. Expression of glial fibrillary acidic protein was determined. GuaDex induction of growth inhibition was fast, showing after less than 5 min incubation while the control cells were not affected even after 50 min incubation. The growth inhibitory effect on PDGCLs spheroids was persistent still showing after 4 weeks post-treatment. The growth inhibition of GuaDex was induced at low µM concentrations while TMZ induced only a slight inhibition at mM concentrations. GuaDex efficacy appears significant and warrants further studies.
Keyphrases
- poor prognosis
- induced apoptosis
- stem cells
- cell cycle arrest
- long non coding rna
- cell therapy
- single cell
- endothelial cells
- diabetic rats
- endoplasmic reticulum stress
- blood brain barrier
- binding protein
- oxidative stress
- high glucose
- cell proliferation
- emergency department
- cell death
- drug induced
- risk assessment
- quantum dots
- neuropathic pain
- high throughput
- spinal cord injury
- preterm birth
- energy transfer
- climate change
- bone marrow