Background: Platelets play an important role in cancer development, metastasis formation, and thrombosis frequently observed in cancer patients. Curcumin has been shown to have antithrombotic and anticancer properties and in combination therapy can enhance effects of anticancer drugs. In cancer cells curcumin can induce caspase-dependent apoptosis, however, it is not known whether this compound can activate caspase pathways and induce or modulate apoptosis in platelets.

Aims: The aim was to analyze whether curcumin can induce platelet apoptosis or modulate apoptosis mediated by BCL-2 protein inhibitor ABT-737.

Methods: Washed platelets were prepared by centrifugation from the whole blood of healthy donors. Phosphatidylserine externalization (PS), αIIbβ3 integrin activation, mitochondrial membrane potential (ΔΨm), and microparticle formation (MP) were analyzed by flow cytometry. Labeled Annexin V, fibrinogen and TMRE were used respectively for PS, integrin activation and ΔΨm measurements. Caspase3 activity was analyzed by Western blot.

Results: Curcumin at 50 µM did not activate caspase 3, however, it inhibited platelet αIIbβ3 integrin activation and induced PS externalization, a fall of ΔΨm, MP formation. Curcumin at lower concentrations (0.5 and 5 µM) had no effects at all measured parameters. The combination of BCL-2 protein inhibitor ABT-737 with curcumin (0.5 and 5 µM) potentiated caspase 3 cleavage, and PS externalization induced by ABT-737. Whereas at 50 µM curcumin inhibited apoptosis induced by ABT-737 (Fig 1.)

Conclusions: Curcumin itself did not induce platelet apoptosis, however it modulated ABT-737-induced apoptosis concentration-dependently by potentiation at low (0.5, 5 µM) doses and inhibition at high (50 µM) doses.
The reported study was funded by RFBR, project number №17-00-00141 (17-00-00139).

[Figure 1. Curcumin at low concentraions potentiated, whereas at high concentration inhibited ABT-737 induced caspase 3 activation.]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/modulation-of-abt-737-induced-platelet-apoptosis-by-curcumin/