Prodigiosin from the supernatant of Serratia marcescens induces apoptosis in haematopoietic cancer cell lines.
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.
Montaner
B
B
Departament de Biologia Cellular i Anatomia Patològica, Unitat de Proliferació i Diferenciació Cellular, Universitat de Barcelona, Barcelona, Spain.
Navarro
S
S
Piqué
M
M
Vilaseca
M
M
Martinell
M
M
Giralt
E
E
Gil
J
J
Pérez-Tomás
R
R
D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002450:Cell Communication; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology; D019169:Jurkat Cells; D051379:Mice; D011353:Prodigiosin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012706:Serratia marcescens / Q000737:chemistry* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011353:Prodigiosin