Studies on the Secondary Metabolites of a Pseudoalteromonas sp. Isolated from Sediments Collected at the Northeastern Coast of Brazil

Abstract

Continuing search for anticancer compounds from the marine environment, we have studied microorganisms that inhabit intertidal sediments of the northeastern Brazilian coast. Of the 32 strains isolated, 13 were selected for biological evaluation of their crude extracts. The acetate extract obtained from a Gram-negative bacterium was strongly active against cancer cell lines with IC(50) values that ranged from 0.04 (HL60 leukemia cells) to 0.26 μg/ml (MDA MB-435 melanoma cells). The bacterium was identified as a Pseudoalteromonas sp. based on 16S rRNA gene sequencing. A bioassay-guided fractionation of the active extract led to the isolation of prodigiosin, a well-known tripyrrole red pigment with immunosuppressive and anticancer activities. Further experiments with ErbB-2 overexpressing cell lines, including HB4a-C3.6 (moderate overexpression), HB4a-C5.2 (high overexpression), and the parental HB4a cell line, were performed. Prodigiosin was moderately active toward HB4a cells with an IC(50) of 4.6 μg/ml, while it was 115 and 18 times more active toward HB4a-C3.6 cells (IC(50) of 0.04 μg/ml) and HB4a-C5.2 (IC(50) of 0.26 μg/ml) cells, respectively. These data suggest that, in spite of its previously described apoptosis-inducing properties, prodigiosin can selectively recognize cells overexpressing ErbB-2, which could be highly appealing in human breast cancer therapy.

Comparative sequence analysis of bacterial symbionts from the marine sponges Geodia cydonium and Ircinia muscarum

“…Concerning Pseudoalteromonas bacterium found in this work in both sponges, it produces as secondary metabolite the prodigiosin, a well-known tripyrrole red pigment with immunosuppressive and anticancer activities, mainly in human breast cancer [15]. Also Proteobacteria species, that we found associated with G. cydonium , resulted widespread in the marine environment.…”

Anti‐Inflammatory Effects of a Methanol Extract from the Marine Sponge Geodia cydonium on the Human Breast Cancer MCF‐7 Cell Line

“…Our recent results showed that a diverse assemblage of bacteria resided in the marine sponge G. cydonium [ 27 ], including Pseudoalteromonas spp. that is reported to produce prodigiosin, a well-known tripyrrolic red pigment with immunosuppressive and anticancer activities, mainly in human breast cancer [ 28 ]. However, to our knowledge, this is the first study testing the biological activity of extracts of this sponge.…”

Anticancer Potential of Compounds from the Brazilian Blue Amazon

“…BRA007 (M23), a strain obtained from Taíba Beach, Ceará state. This study described the cytotoxicity of prodigiosin in a 4-tumor cell line panel and, remarkably, a nearly 100-fold selectivity towards a human breast epithelial cell line, HB4a, stably transfected with cDNA for the receptor tyrosine kinase ErbB-2, in comparison to the parental cell line [139]. Prodigiosin, which is known to induce apoptosis in cancer cells through an intricate, multi-target but not fully characterized mechanism, has been shown to reduce GSK-3β/NAG-1 [140] and JNK/p38/RAD51 [141], as well as to downregulate the expression of members of the IAP family of proteins (▶ Fig.…”