Enoxaparin, Tinzaparin, and Apixaban Modulate Cancer Cell Procoagulant Activity and Viability: Comparison with Quercetin
Abstract
Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.
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BibTeX
@article{baghdadi2026enoxaparin,
title = {{Enoxaparin, Tinzaparin, and Apixaban Modulate Cancer Cell Procoagulant Activity and Viability: Comparison with Quercetin}},
author = {Mohammed A Baghdadi and Pedro Henrique Fernandes Do Carmo Las Casas and Elisabeth Mbemba and Aurélie Rousseau and Prakasha Kempaiah and Andrey A Svistunov and Victoria Bitsadze and Michèle Sabbah and Jawed Fareed and Patrick van Dreden and Varvara Trachana and Eleftheria Lefkou and Grigoris Gerotziafas},
journal = {Cancers},
year = {2026},
month = may,
doi = {10.3390/cancers18111783},
url = {https://hal.science/hal-05847986v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Enoxaparin, Tinzaparin, and Apixaban Modulate Cancer Cell Procoagulant Activity and Viability: Comparison with Quercetin
AU - Mohammed A Baghdadi
AU - Pedro Henrique Fernandes Do Carmo Las Casas
AU - Elisabeth Mbemba
AU - Aurélie Rousseau
AU - Prakasha Kempaiah
AU - Andrey A Svistunov
AU - Victoria Bitsadze
AU - Michèle Sabbah
AU - Jawed Fareed
AU - Patrick van Dreden
AU - Varvara Trachana
AU - Eleftheria Lefkou
AU - Grigoris Gerotziafas
PY - 2026
DA - 2026/05/29
JO - Cancers
DO - 10.3390/cancers18111783
UR - https://hal.science/hal-05847986v1
AB - Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.
SN - 2072-6694
SN - 2072-6694
ER -