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B Montaner, S Navarro, M Piqué, M Vilaseca, M Martinell, E
Giralt, J Gil, R Pérez-Tomás Br J Pharmacol. 2000 Oct ;131
(3):585-93
Prodigiosin from the supernatant of Serratia marcescens
induces apoptosis in haematopoietic cancer cell lines.
Departament de Biologia Cellular i Anatomia Patològica,
Unitat de Proliferació i Diferenciació Cellular, Universitat de
Barcelona, Barcelona, Spain.
The effects of supernatant from the bacterial strain Serratia
marcescens 2170 (CS-2170) on the viability of different
haematopoietic cancer cell lines (Jurkat, NSO, HL-60 and Ramos)
and nonmalignant cells (NIH-3T3 and MDCK) was studied. We
examined whether this cytotoxic effect was due to apoptosis, and
we purified the molecule responsible for this effect and
determined its chemical structure. Using an MTT assay we showed
a rapid (4 h) decrease in the number of viable cells. This
cytotoxic effect was due to apoptosis, according to the
fragmentation pattern of DNA, Hoechst 33342 staining and FACS
analysis of the phosphatidylserine externalization. This
apoptosis was blocked by using the caspase inhibitor Z-VAD.fmk,
indicating the involvement of caspases. Prodigiosin is a red
pigment produced by various bacteria including S. marcescens.
Using mutants of S. marcescens (OF, WF and 933) that do not
synthesize prodigiosin, we further showed that prodigiosin is
involved in this apoptosis. This evidence was corroborated by
spectroscopic analysis of prodigiosin isolated from S.
marcescens. These results indicate that prodigiosin, an
immunosuppressor, induces apoptosis in haematopoietic cancer
cells with no marked toxicity in nonmalignant cells, raising the
possibility of its therapeutic use as an antineoplastic drug.
Mesh-terms: 3T3 Cells; Animals; Antibiotics, Antineoplastic
:: chemistry; Antibiotics, Antineoplastic :: pharmacology;
Apoptosis; Cell Communication; Cell Survival :: drug effects;
HL-60 Cells; Human; Immunosuppressive Agents :: isolation &
purification; Immunosuppressive Agents :: pharmacology; Jurkat
Cells; Mice; Prodigiosin :: chemistry; Prodigiosin :: isolation
& purification; Prodigiosin :: pharmacology; Serratia marcescens
:: chemistry; Serratia marcescens :: physiology; Tumor Cells,
Cultured;
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