Negative Modulation of the Angiogenic Cascade Induced by Allosteric Kinesin Eg5 Inhibitors in a Gastric Adenocarcinoma In Vitro Model.

ABSTRACT: Eg5 is a kinesin essential in bipolar spindle formation, overexpressed in tumours, thus representing a new target in cancer therapy. We aimed at evaluating the anti-cancer activity of Eg5 thiadiazoline inhibitors 2 and 41 on gastric adenocarcinoma cells (AGS), focusing on the modulation of angiogenic signalling. Docking studies confirmed a similar interaction with Eg5 to that of the parent compound K858. Thiadiazolines were also tested in combination with Hesperidin (HSD). Cell cycle analysis reveals a reduction of G1 and S phase percentages when 41 is administered as well as HSD in combination with K858. Western blot reveals Eg5 inhibitors capability to reduce PI3K, p-AKT/Akt and p-Erk/Erk expressions; p-Akt/Akt ratio is even more decreased in HSD+2</

SUBMITTER: Ricci A 

PROVIDER: S-EPMC8840372 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature