Abstract
Tripyrrole molecules have received renewed attention due to reports of numerous biological activities, including antifungal, antibacterial, antiprotozoal, antimalarial, immunosuppressive, and anticancer activities. In a screen of bacterial strains with known toxicities to termites, a red pigment-producing strain, HDZK-BYSB107, was isolated from Chamaecyparis lawsoniana, which grows in Oregon, USA. Strain HDZK-BYSB107 was identified as Serratia marcescens subsp. lawsoniana. The red pigment was identified as prodigiosin using ultraviolet absorption, LC-MS, and 1H-NMR spectroscopy. The bacterial prodigiosin had an inhibitory effect on both Gram-negative and Gram-positive bacteria. The main objective of this study was to explore the anticancer activities and mechanism of strain HDZK-BYSB107 prodigiosin by using human choriocarcinoma (JEG3) and prostate cancer cell lines (PC3) in vitro and JEG3 and PC3 tumor-bearing nude mice in vivo. In vitro anticancer activities showed that the bacterial prodigiosin induced apoptosis in JEG3 cells. In vivo anticancer activities indicated that the prodigiosin significantly inhibited the growth of JEG3 and PC3 cells, and the inhibitory activity was dose and time dependent. The anticancer efficacy of the bacterial prodigiosin on JEG3 and PC3 cells, JEG3 and PC3 tumor exhibited a correlation with the down regulation of the inhibitor of IAP family, including XIAP, cIAP-1 and cIAP-2, and the activation of caspase-9 and caspase-3 accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. The expressions of P53 and Bax/Bcl-2 in JEG3 and PC3 cells were significantly higher than in untreated groups. Our results indicated that the bacterial prodigiosin extracted from C. lawsoniana is a promising molecule due to its potential for therapeutic applications.
Highlights
The many commercially available anticancer drugs can be classified by origin as either chemical synthetic drugs or natural drugs derived from various kinds of organisms [1,2,3]
We described the isolation of a prodigiosin-producing bacterium, HDZK-BYSB107, collected from Port Orford Cedar (POC), C. lawsoniana, in Oregon, USA
The anticancer activity in vitro and in vivo tumor growth inhibition were observed with the treatments of HDZK-BYSB107 prodigiosin
Summary
The many commercially available anticancer drugs can be classified by origin as either chemical synthetic drugs or natural drugs derived from various kinds of organisms [1,2,3]. Natural medicine for cancer therapy has proved to be effective and less toxic on normal cells, with fewer side effects [4]. The discovery of anticancer drugs has mainly resulted from screening of natural products and their analogs [4,6]. Some natural plant metabolites are believed to have anticancer properties; these include several pigments, quinines, and alkaloids [7,8,9,10]. Secondary metabolites from microorganisms are more practical for development as therapeutic agents [11,12,13]
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