A bacterial strain (MS-02-063), which produces red pigment, was discovered from our library established with more than 20000 microorganisms isolated from coastal area of Nagasaki prefecture, Japan. Comparison of 16S rDNA gene sequence of strain MS-02-063 with sequences from GenBank demonstrated that this strain belongs to the g-proteobacterium species. Recent our study has demonstrated that the highly purified red pigment showed potent antimicrobial activity against pathogenic microorganisms such as Staphylococcus aureus and dermatophytes.
1)Prodigiosin (PG) analogues belonging to a family of natural red pigments are characterized by a common pyrrolydipyrrolylmethene skeleton structure with a C-4 methoxy group, and several PG-like pigments have been isolated from certain microorganisms 2-4) including some genera of actinomycetes, Pseudoalteromonas denitrificans, and Serratia marcescens. Representative members of PG analogues are prodigiosin, undecylprodigiosin, cycloprodigiosin hydrochloride, metacycloprodigiosin, and nonylprodigiosin. 5) Some of PG analogues have been reported to have several biological activities such as immunosuppressive, antimalarial, antimicrobial and cytotoxic activities. [6][7][8][9][10][11] Although the exact cytotoxic mechanisms of PG family members are not fully clarified yet, apoptotic mechanism has been proposed for some PG analogues. For instance, it has been reported that cycloprodigiosin hydrochloride induces apoptosis in cancer cells both in vitro and in vivo, with high efficiency in liver cancer, breast cancer cell lines, and colon cancer cells, [12][13][14] with no apparent toxicity to normal cells. 14) PG produced by S. marcescens also induces apoptosis in haematopoietic and gastrointestinal cancer cell lines, but no marked toxicity to non-malignant cell lines. 7,15,16) Considering the high selectivity of PG family members to cancer cells, these pigments may be promising candidates for new anticancer drugs with unique action mechanism. Regarding the structure-activity relationship, it has been reported that a nitrogen-containing heterocyclic A-pyrrole ring with the lone-pair nitrogen electrons in conjugation with the tricyclic frame and a C-4 alkoxy are important for the biological activities of PG analogues.
17)Although there are extensive studies on the cytotoxicities of PG analogues produced by S. marcescens and P. denitrificans, 4,16) only limited information on the bioactivities of PG analogues produced by g-proteobacterium is available. In this study, we examined the cytotoxic effects of PG analogue (PG-L-1), produced by g-proteobacterium (strain MS-02-063) on various cultured cell lines. Since U937 cells showed the highest susceptibility to PG-L-1 cytotoxicity, we conducted detailed analysis of cytotoxic mechanism of PG-L-1 in U937 cells especially in terms of apoptotic cell death. To search for new aspect of biochemical activity of PG-L-1, we also examined the effect of PG-L-1 on the O 2 Ϫ generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated U937 cells.
...