title: 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.
authors.affiliation: Instituto de Ciências do Mar, LABOMAR, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors.forename: Isabelle D B
authors.initials: ID
authors.lastname: Arthaud
authors.forename: Felipe A R
authors.initials: FA
authors.lastname: Rodrigues
authors.forename: Paula C
authors.initials: PC
authors.lastname: Jimenez
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Alysson L
authors.initials: AL
authors.lastname: Angelim
authors.forename: Vânia M M
authors.initials: VM
authors.lastname: Maciel
authors.forename: Edilberto R
authors.initials: ER
authors.lastname: Silveira
authors.forename: Hozana P S
authors.initials: HP
authors.lastname: Freitas
authors.forename: Thiciana S
authors.initials: TS
authors.lastname: Sousa
authors.forename: Otília D L
authors.initials: OD
authors.lastname: Pessoa
authors.forename: Tito M C
authors.initials: TM
authors.lastname: Lotufo
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D010802:Phylogeny; D011353:Prodigiosin / Q000302:isolation & purification / Q000494:pharmacology*; D031161:Pseudoalteromonas / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D011353:Prodigiosin