Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines.
Prodigiosin is a bacterial red pigment with cytotoxic properties and potential antitumor activity that has been tested against different cancerous cells. In this study we report the effect and mechanisms of action of prodigiosin against different human neuroblastoma cell lines: SH-SY5Y, LAN-1, IMR-32 (N-type) and SK-N-AS (S-type). We compare the anticancerous effect of prodigiosin with that of cisplatin at different concentrations during 24 h of exposure. Prodigiosin is more potent, with IC50 values lower than 1.5 microM in N-type neuroblastoma cells and around 7 microM in the S-type neuroblastoma cell line. We describe prodigiosin as a proton sequestering agent that destroys the intracellular pH gradient, and propose that its main cytotoxic effect could be related to its action on mitochondria, where it exerts an uncoupling effect on the electronic chain transport of protons to mitochondrial ATP synthase. As a result of this action, ATP production is reduced but without decreasing in oxygen consumption. This mechanism of action differs from those induced by conventional chemotherapeutic drugs, suggesting a possible role for prodigiosin to enhance the effect of antitumor agents in the treatment of neuroblastoma.
Francisco
Roser
R
Unitat de Bioquímica, Departament de Cincies Fisiolgiques II, Campus de Bellvitgte, IDIBELL-Universitat de Barcelona, Spain.
Pérez-Tomás
Ricardo
R
Gimènez-Bonafé
Pepita
P
Soto-Cerrato
Vanessa
V
Giménez-Xavier
Pol
P
Ambrosio
Santiago
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma; D010101:Oxygen Consumption; D011353:Prodigiosin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000255:Adenosine Triphosphate; D011353:Prodigiosin; D002945:Cisplatin