Our group has recently demonstrated that K858, an inhibitor of motor kinesin Eg5, determines important antiproliferative and apoptotic effects on breast cancer, prostatic cancer, melanoma and glioblastoma cells. Since high levels of kinesin Eg5 expression have been correlated to a poor prognosis in laryngeal carcinoma, we decided to test the anti-cancer activity of K858 toward this tumor, which belongs to the group of head and neck squamous cell carcinomas (HNSCCs). Even because these cancers are characterized by low responsiveness to therapy. The effects of K858 on the proliferation and assembly of mitotic spindles of three human HNSCC cell lines were studied using cytotoxicity assay and tubulin immunofluorescence respectively. The effect of K858 on the cell cycle was analyzed by FACS. Cyclin B1 expression was studied using both immunofluorescence and Western blot. The quantification of several apoptosis and invasion markers was assessed by Western blot. An invasion assay was used to quantify the ability of tumor cells to infiltrate extracellular matrix. We tested the effects of K858 on three human HNSCC cell lines and found that K858 significantly inhibited replication. K858 impaired development of normal bipolar mitotic spindles, blocked the cell cycle in G2 and caused cytoplasmic accumulation of cyclin B1. Consequently, K858 activated apoptosis. In addition, K858 was able to reverse the epithelial-mesenchymal transition and to inhibit cell migration and extracellular matrix invasion. The data described confirm that kinesin Eg5 is an interesting target for new anti-cancer strategies and suggest that this compound may be a powerful tool for an alternative therapeutic approach to HNSCCs.

The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells / Nicolai, Alice; Taurone, Samanta; Carradori, Simone; Artico, Marco; Greco, Antonio; Costi, Roberta; Scarpa, Susanna. - In: INVESTIGATIONAL NEW DRUGS. - ISSN 0167-6997. - (2022). [10.1007/s10637-022-01238-2]

The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells

Nicolai, Alice
Primo
;
Taurone, Samanta
Secondo
;
Artico, Marco;Greco, Antonio;Costi, Roberta
Penultimo
;
Scarpa, Susanna
Ultimo
2022

Abstract

Our group has recently demonstrated that K858, an inhibitor of motor kinesin Eg5, determines important antiproliferative and apoptotic effects on breast cancer, prostatic cancer, melanoma and glioblastoma cells. Since high levels of kinesin Eg5 expression have been correlated to a poor prognosis in laryngeal carcinoma, we decided to test the anti-cancer activity of K858 toward this tumor, which belongs to the group of head and neck squamous cell carcinomas (HNSCCs). Even because these cancers are characterized by low responsiveness to therapy. The effects of K858 on the proliferation and assembly of mitotic spindles of three human HNSCC cell lines were studied using cytotoxicity assay and tubulin immunofluorescence respectively. The effect of K858 on the cell cycle was analyzed by FACS. Cyclin B1 expression was studied using both immunofluorescence and Western blot. The quantification of several apoptosis and invasion markers was assessed by Western blot. An invasion assay was used to quantify the ability of tumor cells to infiltrate extracellular matrix. We tested the effects of K858 on three human HNSCC cell lines and found that K858 significantly inhibited replication. K858 impaired development of normal bipolar mitotic spindles, blocked the cell cycle in G2 and caused cytoplasmic accumulation of cyclin B1. Consequently, K858 activated apoptosis. In addition, K858 was able to reverse the epithelial-mesenchymal transition and to inhibit cell migration and extracellular matrix invasion. The data described confirm that kinesin Eg5 is an interesting target for new anti-cancer strategies and suggest that this compound may be a powerful tool for an alternative therapeutic approach to HNSCCs.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1623472
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