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Article

Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis

1
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia
2
Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 109029 Moscow, Russia
3
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Isabella Russo
Int. J. Mol. Sci. 2021, 22(10), 5405; https://doi.org/10.3390/ijms22105405
Received: 16 April 2021 / Revised: 17 May 2021 / Accepted: 18 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Molecular Research on Platelet Function in Disease)
Curcumin is a natural bioactive component derived from the turmeric plant Curcuma longa, which exhibits a range of beneficial activities on human cells. Previously, an inhibitory effect of curcumin on platelets was demonstrated. However, it is unknown whether this inhibitory effect is due to platelet apoptosis or procoagulant platelet formation. In this study, curcumin did not activate caspase 3-dependent apoptosis of human platelets, but rather induced the formation of procoagulant platelets. Interestingly, curcumin at low concentration (5 µM) potentiated, and at high concentration (50 µM) inhibited ABT-737-induced platelet apoptosis, which was accompanied by inhibition of ABT-737-mediated thrombin generation. Platelet viability was not affected by curcumin at low concentration and was reduced by 17% at high concentration. Furthermore, curcumin-induced autophagy in human platelets via increased translocation of LC3I to LC3II, which was associated with activation of adenosine monophosphate (AMP) kinase and inhibition of protein kinase B activity. Because curcumin inhibits P-glycoprotein (P-gp) in cancer cells and contributes to overcoming multidrug resistance, we showed that curcumin similarly inhibited platelet P-gp activity. Our results revealed that the platelet inhibitory effect of curcumin is mediated by complex processes, including procoagulant platelet formation. Thus, curcumin may protect against or enhance caspase-dependent apoptosis in platelets under certain conditions. View Full-Text
Keywords: platelets; apoptosis; autophagy; procoagulant activity; thrombin platelets; apoptosis; autophagy; procoagulant activity; thrombin
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MDPI and ACS Style

Rukoyatkina, N.; Shpakova, V.; Sudnitsyna, J.; Panteleev, M.; Makhoul, S.; Gambaryan, S.; Jurk, K. Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis. Int. J. Mol. Sci. 2021, 22, 5405. https://doi.org/10.3390/ijms22105405

AMA Style

Rukoyatkina N, Shpakova V, Sudnitsyna J, Panteleev M, Makhoul S, Gambaryan S, Jurk K. Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis. International Journal of Molecular Sciences. 2021; 22(10):5405. https://doi.org/10.3390/ijms22105405

Chicago/Turabian Style

Rukoyatkina, Natalia, Valentina Shpakova, Julia Sudnitsyna, Michael Panteleev, Stephanie Makhoul, Stepan Gambaryan, and Kerstin Jurk. 2021. "Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis" International Journal of Molecular Sciences 22, no. 10: 5405. https://doi.org/10.3390/ijms22105405

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