In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacetylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10.

The 2,4-diacetylphloroglucinol (DAPG), a polyketide metabolite extracted from Pseudomonas aeruginosa strain FP10, exhibited selective cytoxicity against lung (A549), breast (MDA MB-231), cervical (HeLa) and colon (HCT-15) cancer cells in differential and dose-dependent manner. The anticancer and antimetastatic activities of DAPG were mediated by the inhibition of ROS, NF-κB, Bcl-2, MMP-2, VEGF and primary inflammatory mediators such as TNF-α, IL-6, IL-1β and NO. The DAPG induced apoptosis in cancer cells by intrinsic and extrinsic pathways via the release of cytochrome-C, upregulation of Bax and the activation of caspases and also, exhibited anti-inflammatory activity by the inhibition of LPS-inflammed cell proliferation of macrophage (Raw 264.7), monocytic cells (THP-1) and peripheral blood mononuclear cells (PBMCs). Results further confirmed that the DAPG inhibited the primary inflammatory mediators in cancer cells and inflammed immune cells through the down regulation of NF-κB. In the present study, for the first time, antiproliferative, proapoptotic, antimetastatic and anti-inflammatory activities of DAPG in various cancer cells and inflammation-induced immune cells have been reported.