Franciso 2007 Eur J Pharmacol

Franciso R, Perez-Tomas R, Gimenez-Bonafe P, Soto-Cerrato V, Gimenez-Xavier P, Santiago A (2007) Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines. Eur J Pharmacol 572: 111-119.

» PMID: 17678643

Franciso R, Perez-Tomas R, Gimenez-Bonafe P, Soto-Cerrato V, Gimenez-Xavier P, Santiago A (2007) Eur J Pharmacol

Abstract: 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 μM in N-type neuroblastoma cells and around 7 μM 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. • Keywords: Neuroblastoma, Prodigiosin, Cisplatin, Apoptosis

Labels:

Stress:Cancer; Apoptosis; Cytochrome c"Cancer; Apoptosis; Cytochrome c" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. 

Preparation: Intact cells  Enzyme: Complex V; ATP Synthase"Complex V; ATP Synthase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: ATP; ADP; AMP; PCr"ATP; ADP; AMP; PCr" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.  Coupling state: ROUTINE 

HRR: Oxygraph-2k