Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents
journal contributionposted on 2012-05-19, 00:00 authored by Tamara P. Kondratyuk, Eun-Jung Park, Rui Yu, Richard B. van Breemen, Ratnakar N. Asolkar, Brian T. Murphy, William Fenical, John M. Pezzuto
Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects.
This work was supported by program project grant P01 CA48112 (to JP) and CA44848 (to WF) awarded by the National Cancer Institute.
Publisher Statement© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). doi:10.3390/md10020451