| Literature DB >> 33925528 |
Hajer Ziouziou1,2, Clément Paris1, Sébastien Benizri3, Thi Khanh Le1, Claudia Andrieu1, Dang Tan Nguyen1, Ananda Appavoo3, David Taïeb1,4, Frédéric Brunel5, Ridha Oueslati2, Olivier Siri5, Michel Camplo5, Philippe Barthélémy3, Palma Rocchi1.
Abstract
Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5'-(2',3'-dioleoyl)uridine]-N',N',N'-trimethylammonium tosylate) and DOU-PEG2000 (5'-PEG2000-2',3'-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy.Entities:
Keywords: dialkoxyphenazine; nanoformulation; nucleolipid; prostate cancer
Year: 2021 PMID： 33925528 DOI： 10.3390/pharmaceutics13050623
Source DB: PubMed Journal: Pharmaceutics ISSN： 1999-4923 Impact factor: 6.321