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.
Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India.
Vijay Kumar
VK
Veena
Ravindra Naik
RN
Popavath
Kamaraj
K
Kennedy
Natarajan
N
Sakthivel
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D061065:Polyketides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011550:Pseudomonas aeruginosa / Q000737:chemistry*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D061065:Polyketides; C059817:2,4-diacetylphloroglucinol; D010696:Phloroglucinol