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Published on: January 20, 2014
Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines
Roser Francisco1, Ricardo Pérez-Tomás, Pepita Gimènez-Bonafé
1Unitat de Bioquímica, Departament de Cincies Fisiolgiques II, Campus de Bellvitgte, IDIBELL-Universitat de Barcelona, Spain.
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 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.
Insights
Prodigiosin, a bacterial pigment, shows potent anticancer effects against neuroblastoma cells, outperforming cisplatin. Its unique mechanism involves disrupting mitochondrial function, offering potential for novel neuroblastoma treatments.
Area of Science:
- Microbiology
- Biochemistry
- Oncology
Background:
- Prodigiosin is a bacterial red pigment known for its cytotoxic properties.
- It has demonstrated potential antitumor activity against various cancer cells.
- Neuroblastoma is a significant pediatric cancer requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects and mechanisms of action of prodigiosin on human neuroblastoma cell lines.
- To compare the anticancer efficacy of prodigiosin with cisplatin.
- To elucidate the specific molecular targets and pathways affected by prodigiosin.
Main Methods:
- Treatment of neuroblastoma cell lines (SH-SY5Y, LAN-1, IMR-32, SK-N-AS) with prodigiosin and cisplatin.
- Determination of half-maximal inhibitory concentration (IC50) values.
- Analysis of intracellular pH gradients and mitochondrial function, including oxygen consumption and ATP production.
Main Results:
- Prodigiosin exhibited potent cytotoxicity against N-type (IC50 < 1.5 microM) and S-type (IC50 ~ 7 microM) neuroblastoma cells.
- Prodigiosin acts as a proton sequestering agent, disrupting the intracellular pH gradient.
- Mitochondrial uncoupling of the electron transport chain was observed, reducing ATP production without affecting oxygen consumption.
Conclusions:
- Prodigiosin demonstrates significant anticancer potential against neuroblastoma, with a distinct mechanism of action.
- Its ability to disrupt mitochondrial function suggests a novel therapeutic approach.
- Prodigiosin may serve as a valuable agent to enhance the efficacy of existing antitumor therapies for neuroblastoma.
