Enhanced Platelet Activation Induced by Palbociclib Treatment in MCF-7 Breast Cancer Cells
DOI:
https://doi.org/10.35516/jjps.v18i1.2459Keywords:
Confocal microscopy, Flow cytometry, MCF-7, Palbociclib, Platelets, P-selectinAbstract
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.
References
Gasic G. J., Gasic T. B., and Stewart C. C. Antimetastatic effects associated with platelet reduction. Proceedings of the National Academy of Sciences. 1968; 61(1):46-52. DOI: https://doi.org/10.1073/pnas.61.1.46
Labelle M., Begum S., and Hynes R. O. Platelets guide the formation of early metastatic niches. Proceedings of the National Academy of Sciences. 2014; 111(30):E3053-E3061. DOI: https://doi.org/10.1073/pnas.1411082111
Bambace N. and Holmes C. The platelet contribution to cancer progression. Journal of Thrombosis and Haemostasis. 2011; 9(2):237-249. DOI: https://doi.org/10.1111/j.1538-7836.2010.04131.x
Shu L., Lin S., Zhou S., and Yuan T. Glycan-Lectin interactions between platelets and tumor cells drive hematogenous metastasis. Platelets. 2024; 35(1):2315037. DOI: https://doi.org/10.1080/09537104.2024.2315037
Zarà M., Canobbio I., Visconte C., Canino J., Torti M., and Guidetti G. F. Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells. Cellular Signalling. 2018; 48:45-53. DOI: https://doi.org/10.1016/j.cellsig.2018.04.008
Manimaran D., Elangovan N., and Palanisamy V. Anti-Tumorigenic Impact of Nano-Formulated Peptide HIF-Alpha Therapy by DMBA Induced Mammary Carcinoma in Rodent Type. Jordan Journal of Pharmaceutical Sciences. 2024; 17(4):783-793. DOI: https://doi.org/10.35516/jjps.v17i4.2482
Kzar H. H., Al-Gazally M. E., and Wtwt M. A. Everolimus loaded NPs with FOL targeting: preparation, characterization and study of its cytotoxicity action on MCF-7 breast cancer cell lines. Jordan Journal of Pharmaceutical Sciences. 2022; 15(1):25-39. DOI: https://doi.org/10.35516/jjps.v15i1.286
Al-Samydai A., Abu Hajleh M. N., Al-Sahlawi F., Nsairat H., Khatib A. A., Alqaraleh M., and Ibrahim A. K. Advancements of metallic nanoparticles: A promising frontier in cancer treatment. Science Progress. 2024; 107(4):00368504241274967. DOI: https://doi.org/10.1177/00368504241274967
Al-Sahlawi F., Alabdali A. Y., Chinnappan S., Al-Samydai A., and Maki M. A. Polymer-based nanoparticles in targeted cancer therapy: a review. Journal of Applied Pharmaceutical Science. 2024; 14(9):57-68. DOI: https://doi.org/10.7324/JAPS.2024.172227
Osanloo M., Yousefpoor Y., Alipanah H., Ghanbariasad A., Jalilvand M., and Amani A. In-vitro Assessment of essential oils as Anticancer Therapeutic agents: a systematic literature review. Jordan Journal of Pharmaceutical Sciences. 2022; 15(2):173-203. DOI: https://doi.org/10.35516/jjps.v15i2.319
Abdel-Razeq H., Mansour A., and Jaddan D. Breast cancer care in Jordan. JCO Global Oncology. 2020; 6:260-268. DOI: https://doi.org/10.1200/JGO.19.00279
Estepa-Fernández A., García-Fernández A., Lérida-Viso A., Blandez J. F., Galiana I., Sancenon-Galarza F., et al. Combination of palbociclib with navitoclax-based therapies enhances in vivo antitumoral activity in triple-negative breast cancer. Pharmacological Research. 2023; 187:106628. DOI: https://doi.org/10.1016/j.phrs.2022.106628
West M. T., Smith C. E., Kaempf A., Kohs T. C., Amirsoltani R., Ribkoff J., et al. CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real‐world practice. European Journal of Haematology. 2021; 106(5):634-642. DOI: https://doi.org/10.1111/ejh.13590
Raschi E., Fusaroli M., Ardizzoni A., Poluzzi E., and De Ponti F. Thromboembolic events with cyclin-dependent kinase 4/6 inhibitors in the FDA adverse event reporting system. Cancers. 2021; 13(8):1758. DOI: https://doi.org/10.3390/cancers13081758
Gervaso L., Montero A. J., Jia X., and Khorana A. A. Venous thromboembolism in breast cancer patients receiving cyclin‐dependent kinase inhibitors. Journal of Thrombosis and Haemostasis. 2020; 18(1):162-168. DOI: https://doi.org/10.1111/jth.14630
Watson G. A., Deac O., Aslam R., O'Dwyer R., Tierney A., Sukor S., et al. Real-world experience of palbociclib-induced adverse events and compliance with complete blood count monitoring in women with hormone receptor–positive/HER2-negative metastatic breast cancer. Clinical Breast Cancer. 2019; 19(1):e186-e194. DOI: https://doi.org/10.1016/j.clbc.2018.09.002
Beachler D. C., de Luise C., Jamal-Allial A., Yin R., Taylor D. H., Suzuki A., et al. Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study. BMC Cancer. 2021; 21:1-13. DOI: https://doi.org/10.1186/s12885-021-07790-z
Abbas M. M., Kandil Y. İ., and Abbas M. A. R-(-)-carvone attenuated doxorubicin-induced cardiotoxicity in vivo and potentiated its anticancer toxicity in vitro. Balkan Medical Journal. 2020; 37(2):98. DOI: https://doi.org/10.4274/balkanmedj.galenos.2019.2019.7.117
Gomes M. N., Fru P., Augustine T. N., Moyo D., Chivandi E., and Daniels W. M. Differential expression of platelet activation markers, CD62P and CD63, after exposure to breast cancer cells treated with Kigelia africana, Ximenia caffra, and Mimusops zeyheri seed oils in vitro. Nutrition and Cancer. 2022; 74(8):3035-3050. DOI: https://doi.org/10.1080/01635581.2022.2032215
Pather K., and Augustine T. Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo. Scientific Reports. 2020; 10(1):19256. DOI: https://doi.org/10.1038/s41598-020-75779-y
Schwarz S., Gockel L. M., Naggi A., Barash U., Gobec M., Bendas G., et al. Glycosaminoglycans as tools to decipher the platelet-tumor cell interaction: a focus on P-selectin. Molecules. 2020; 25(5):1039. DOI: https://doi.org/10.3390/molecules25051039
Mitrugno A., Williams D., Kerrigan S. W., and Moran N. A novel and essential role for FcγRIIa in cancer cell–induced platelet activation. Blood, The Journal of the American Society of Hematology. 2014; 123(2):249-260. DOI: https://doi.org/10.1182/blood-2013-03-492447
Koene R. J., Prizment A. E., Blaes A., and Konety S. H. Shared risk factors in cardiovascular disease and cancer. Circulation. 2016; 133(11):1104-1114. DOI: https://doi.org/10.1161/CIRCULATIONAHA.115.020406
Fernandes C. J., Morinaga L. T., Alves Jr J. L., Castro M. A., Calderaro D., Jardim C. V., et al. Cancer-associated thrombosis: the when, how, and why. European Respiratory Review. 2019; 28(151). DOI: https://doi.org/10.1183/16000617.0119-2018
Grover S. P., Hisada Y. M., Kasthuri R. S., Reeves B. N., and Mackman N. Cancer therapy–associated thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2021; 41(4):1291-1305. DOI: https://doi.org/10.1161/ATVBAHA.120.314378
Sbrana S., Della Pina F., Rizza A., Buffa M., De Filippis R., Gianetti J., et al. Relationships between optical aggregometry (type Born) and flow cytometry in evaluating ADP‐induced platelet activation. Cytometry Part B: Clinical Cytometry: The Journal of the International Society for Analytical Cytology. 2008; 74(1):30-39. DOI: https://doi.org/10.1002/cyto.b.20360
Tera Y., Azzam H., Abousamra N., Zaki M., Eltantawy A., Awad M., et al. Platelet activation and platelet indices as markers for disease progression in women with breast cancer: Platelets and prognosis of breast cancer. Archives of Breast Cancer. 2022: 346-353. DOI: https://doi.org/10.32768/abc.202293346-353
Bendas G., and Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. International Journal of Cell Biology. 2012; 2012(1):676731. DOI: https://doi.org/10.1155/2012/676731
Yap M. L., McFadyen J. D., Wang X., Zia N. A., Hohmann J. D., Ziegler M., et al. Targeting activated platelets: a unique and potentially universal approach for cancer imaging. Theranostics. 2017; 7(10):2565 DOI: https://doi.org/10.7150/thno.19900
Zuo X-X., Yang Y., Zhang Y., Zhang Z-G., Wang X-F., and Shi Y-G. Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin α2β1-contacting-mediated activation of Wnt-β-catenin pathway. Cell Communication and Signaling. 2019; 17:1-15. DOI: https://doi.org/10.1186/s12964-019-0464-x
Castanheira N. M., Spanhofer A. K., Wiener S., Bobe S., and Schillers H. Uptake of platelets by cancer cells and recycling of the platelet protein CD42a. Journal of Thrombosis and Haemostasis. 2022; 20(1):170-181. DOI: https://doi.org/10.1111/jth.15543