Biological Potential and Mechanism of Prodigiosin from Serratia marcescens Subsp. lawsoniana in Human Choriocarcinoma and Prostate Cancer Cell Lines

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.

Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights

“…In mammals, the 'caspases' are a highly specific class of cysteine proteases 57 that can initiate/suppress programmed cell death via activation/deactivation of several proteins 91,92 . Treatment with prodigiosin alone and its combination with PU-H71 increased the level of caspase 8 and 9 transcription in contrast to PU-H71, which is in agreement with Li and his colleagues in 2018 93 , stating that the proposed anticancer effects of prodigiosin is caspase-dependent. PU-H71 did not increase caspase 9 level opposing to a previous study that reported the activation of caspase 9 upon using PU-H71 94 .…”

“…PU-H71 did not increase caspase 9 level opposing to a previous study that reported the activation of caspase 9 upon using PU-H71 94 . Noticeably, prodigiosin displayed multimodal anticancer potency as a result of caspase-dependent and -independent induction of apoptosis, activation of protein kinase pathways, and induction of cell cycle arrest 93 . Consistent with previous findings, we elucidated that prodigiosin induces mitochondrial-dependent apoptosis by the upregulation of BAX and caspase 9 transcription levels.…”

In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6

“…5D). Recent literature reported that supernatant metabolites of H. salinarum IBRC M10715 and red pigment-producing HDZK-BYSB107 were able to induce apoptosis in prostate cells via upregulation of caspase 3 20,21 . Figure 6.…”

Novel Efficient Bioprocessing of Marine Chitins into Active Anticancer Prodigiosin

“…Thus, the investigation of natural anticancer drugs has received much interest. Prodigiosin was investigated as a potent natural anticancer agent since it showed strong inhibition against a wide range of human cancer cell lines but lower toxicity toward normal cells [41]. The mechanisms of anticancer activity of prodigiosin were reported in previous studies [41][42][43].…”

“…Prodigiosin was investigated as a potent natural anticancer agent since it showed strong inhibition against a wide range of human cancer cell lines but lower toxicity toward normal cells [41]. The mechanisms of anticancer activity of prodigiosin were reported in previous studies [41][42][43]. Prodigiosin induces apoptosis in various human cancer cells [42], and some possible mechanisms were prosed that prodigiosin as mitogen-activated protein kinase regulators, cell cycle inhibitors, DNA cleavage agents, and pH modulators [43].…”