6BrCaQ is a promising anti-cancer agent derived from novobiocin, which has been shown to inhibit Hsp90. 6BrCaQ was loaded into nanometer-scaled phospholipid vesicles (liposomes) suitable for drug delivery to solid tumors. The effective incorporation of the drug within the phospholipid bilayer was investigated by differential scanning calorimetry. Liposomal 6BrCaQ showed good activity on PC-3 cell lines in vitro in terms of apoptosis induction and cell growth arrest in G2/M. Liposomes containing 6BrCaQ were also shown to slow down migration of PC-3 cells in presence of chemokine ligand 2 and to synergize with doxorubicin. Several Hsp90 targeting molecules like geldanamycin induce accumulation of Hsp70, leading to cytoprotection and often correlated with poor prognosis. In this study, we did not report any Hsp70 induction after treatment with liposomal 6BrCaQ but a decrease in Hsp90 and CDK-4 protein expression, indicating an effect on the chaperon machinery. Liposomal encapsulation of 6BrCaQ revealed promising anti-cancer effects and a better understanding of its mechanism of action.
Keywords: Apoptosis; Cell cycle; Hsp90; Liposomes; Migration; Novobiocin analog.
Copyright © 2016. Published by Elsevier B.V.