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

• Main Authors: Dan Li, Jun Liu, Xin Wang, Di Kong, Wei Du, Hongbo Li, Chung-Yun Hse, Todd Shupe, Dongpo Zhou, Kai Zhao
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Serratia marcescens</i> subsp. <i>lawsoniana</i>; prodigiosin; secondary metabolites; human choriocarcinoma cell lines and human prostate cancer cell lines; anticancer activities and mechanism
• Online Access: https://www.mdpi.com/1422-0067/19/11/3465

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 <i>Chamaecyparis lawsoniana</i>, which grows in Oregon, USA. Strain HDZK-BYSB107 was identified as <i>Serratia marcescens</i> subsp. <i>lawsoniana</i>. 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 <i>C. lawsoniana</i> is a promising molecule due to its potential for therapeutic applications.