Xiaosi Lin,Le Dong,Qing Miao,Zhaobin Huang,Fang Wang
Prodiginines have been studied extensively for their anticancer activity, however, the majority of the research has focused on prodigiosin. In this study, cycloheptylprodigiosin (S-1) is extracted from marine bacterium Spartinivicinus ruber MCCC 1K03745 T , and its anticancer property was investigated. It exhibits remarkable cytotoxicity against a panel of human lung cancer cell lines, with the IC 50 values ranging from 84.89 nM to 661.2 nM. After 6 hours of treatment, S-1 gradually accumulates on mitochondria and lysosomes. While lower doses of S-1 induce cell cycle arrest, treatment with higher doses results in cell death in apoptotic independent manner in both NCI-H1299 and NCI-H460 cell lines. Interestingly, treatment with S-1 leads to the accumulation of LC3B-II via pathways that vary among different cell lines. In addition to its role as an autophagy inhibitor, S-1 also promotes autophagy initiation as demonstrated by the increment of EGFP fragment in the EGFP-LC3 degradation assay, however, inhibition of autophagy does not rescue cells from death induced by S-1. Mechanistically, S-1 impairs autophagic flux through disrupting acidic lysosomal pH and blocking the maturation of cathepsin D. Moreover, treatment with S-1 enhanced secretion of both pro- and mature forms of cathepsin D, coincident with disintegration of trans-Golgi network. Interestingly, S-1 does not induce ferroptosis, pyroptosis or necroptosis in NCI-H1299 cells. However, treatment of NCI-H460 cells with S-1 induces methuosis, which can be suppressed by Rac1 inhibitor EHT 1864. Our data demonstrate that S-1 is an effective anticancer agent with potential therapeutic application.
Cycloheptylprodigiosin is a promising anticancer candidate that induces cancer cell death accompanied by severe Golgi stress. Although the soybean oil-based optimized MB2216 medium produced a total prodiginine titer approximately three times that of the basal MB2216 medium, the overall production level remained limited. In addition, a substantial fraction of the pigments partitioned into floating oil droplets, hindering efficient recovery by simple centrifugation. In this study, a novel medium was rationally formulated based on genomic insights derived from homology analysis of conserved biosynthetic genes involved in cycloheptylprodigiosin production inSpartinivicinus ruberMCCC 1K03745T. Sequential optimization through single-factor experiments, full factorial designs, steepest ascent experiments and response surface methodology identified an optimal medium consisting of peptone (5 g/L), yeast extract (1 g/L), peanut meal (7.611 g/L), and L-Proline (0.695 g/L) prepared in seawater at pH 7.6. Under the optimized conditions, the total prodiginine titer reached 53.33 mg/L, which was 11.37 times that of the basal MB2216 medium and 3.29 times that of the soybean oil-based MB2216 medium. Moreover, the pigment-associated biomass could be efficiently recovered by centrifugation. This study provides a genomics-informed strategy for improving prodiginine production inS. ruberand facilitates downstream pigment recovery.
危险品化学品经营许可证（带存储）