Extracellular vesicles (EVs) fromhuman cerebral endothelial cells grown in oxygen-glucose deprivation conditions exhibit potent anti-cancer activity against a wide array of human cancer cell lines with no effect on benign cells
Recommended Citation
Moonka D. Extracellular vesicles (EVs) fromhuman cerebral endothelial cells grown in oxygen-glucose deprivation conditions exhibit potent anti-cancer activity against a wide array of human cancer cell lines with no effect on benign cells. J Extracell Vesicles 2025; 14.
Document Type
Conference Proceeding
Publication Date
10-8-2025
Publication Title
J Extracell Vesicles
Keywords
glucose, oxygen, A-549 cell line, A2780 cell line, antineoplastic activity, cell viability assay, colon cell, conference abstract, controlled study, endothelium cell, exosome, HCE cell line (colon epithelium), HCT 116 cell line, Hep 3B2.1-7 cell line, Hep-G2 cell line, human, human cell, liver cell carcinoma, lung alveolus cell, MDA-MB-231 cell line, MDA-MB-468 cell line, neoplastic cell transformation, NIH 3T3 cell line, ovary cell, OVCAR-3 cell line, PANC-1 cell line, pancreas cell, THLE-2 cell line, tissue culture, ultracentrifugation
Abstract
Introduction: After observing a patient with advanced hepatocellular carcinoma (HCC) experience complete resolution of the HCC after experiencing an ischaemic stroke, we hypothesized that EVs from stroke patients could have anti-neoplastic activity. We evaluated the anti-cancer activity of stroke-EVs as well as the anti-cancer activity of EVs fromhuman cerebral endothelial cells (hCEC) exposed to oxygen-glucose deprivation to mimic stroke conditions in tissue culture. Methods: All EVs in all experiments were isolated by ultracentrifugation. Plasma EVs from three patients experiencing ischaemic stroke (stroke-EVs) were tested at 108 particles/mL against HCC cell lines, HepG2 and Hep3B, for five days using the MTT cell viability assay. Each assay consisted of five duplicate wells. EVs from healthy patients were also evaluated, and the benign liver cell line, THLE-2, was used as a non-cancerous control. EVs obtained from hCEC cells exposed to oxygenglucose deprivation (OGD-EVs), to simulate stroke conditions, were tested against all three lines and an array of other human cancer cell lines. Results: Plasma EVs from healthy controls significantly increased viability of all three cell lines compared to untreated cells: HepG2 (113%-171%: p < 0.001), Hep3B (165%-170%: p < 0.001), THLE-2 (151%-160%: p < 0.001). Stroke-EVs from three stroke patients inhibited HepG2 viability by 89%, 90% and 75% (p < 0.001) compared to untreated cells. The stroke-EVs inhibited Hep3B viability by 75%, 81% and 72% (p < 0.001). Stroke-EVs did not inhibit THLE-2 cells (+15%, +5.4%, -2%). OGD-EVs (108 p/mL) from hCEC cells generated in exosome free media inhibited HepG2 cells by 73.1% (p < 0.001) and Hep3B cells by 76.5%. EVs from hCEC cells not exposed to OGD had no effect on any cells, benign or malignant, and no EVs inhibited THLE-2 cells. At 108 particles/mL, OGD-EVs inhibited pancreas cells (Panc-1, 62%), lung cells (A549, 74%), breast cells (MDA-MB-468, 84%; MDA-MB-231, 77%), prostate cells (PC3, 78%), colon cells (HCT-116, 64%), and ovarian cells (A2780, 65%; OVCAR-3, 64%). All differences were significant at p < 0.001. The OGD-EVs did not affect the multi-resistant ovarian cell line, A2780-cis, and the benign fibroblast cell line NIH-3T3. Summary/Conclusion: Conclusions: OGD-EVs from HCEC cells represent a potential therapeutic option for patients with HCC and other malignancies.
Volume
14
