Enhanced Platelet Activation Induced by Palbociclib Treatment in MCF-7 Breast Cancer Cells

Background and aim: The crosstalk between platelets and cancer cells is bidirectional. Cancer cells can activate platelets, a process known as "tumor cell-induced platelet aggregation". On the other hand, platelets provide essential assistance to tumor cells by helping them adhere to blood vessels, facilitating their escape from the bloodstream, and enabling their spread to distant tissues. This study investigates the effect of Palbociclib, an FDA-approved cyclin-dependent kinase 4 and 6 inhibitor, on breast cancer-cell-induced platelet activation. Method: Platelet activation, as indicated by the expression of CD62P (P-selectin), was assessed by flow cytometry. In addition, platelet attachment to MCF-7 cancer cells was studied using confocal microscopy. Results: Palbociclib's half-maximal concentration (IC50) was found to be 19.54 µM after 72 h. About 36.9% + 0.98 of platelets were activated by untreated MCF-7. Pretreatment of MCF-7 cells with Palbociclib (9.75 µM equivalent to 1/2 IC50) increased platelet activation significantly by 63.3% + 8.85 (P<0.01) while 4.87 µM Palbociclib (1/4 IC50) increased platelet activation by 43.0% + 2.83 with no significant difference compared to untreated cells. Confocal microscopy results suggest the presence of a direct interaction between breast cancer cells and platelets. Conclusion: Palbociclib increased tumor-induced platelet activation in MCF-7 hormone-positive breast cancer cell line.