Novel Phenazine 5,10-Dioxides Release •OH in Simulated Hypoxia and Induce Reduction of Tumour Volume In Vivo

Joint Authors

Pintos, Cristina
Monge, Antonio
Pacheco, José Pedro
Cerecetto, Hugo
Cascante, Marta
Pachón, Gisela
Raymondo, Stella
Olea-Azar, Claudio
López de Ceráin, Adela
Cabrera, Mauricio
González, Mercedes
Rodríguez, Jorge
Arredondo, Carolina
Lavaggi, María L.

Source

ISRN Pharmacology

Issue

Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-11, 11 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2011-06-22

Country of Publication

Egypt

No. of Pages

11

Main Subjects

Pharmacy, Health & Medical Sciences
Pharmacology

Abstract EN

Phenazine 5,10-dioxides (PDOs) are a new class of bioreductive cytotoxins, which could act towards tumours containing hypoxic regions.

The PDOs selective-hypoxic bioreduction was probed in vitro; however, the mechanism of action has not been completely explained.

Besides, PDOs in vivo antitumour activities have not been demonstrated hitherto.

We study the mechanism of hypoxic/normoxic cytotoxicity of PDO representative members.

Electron spin resonance is used to confirm •OH production, alkaline comet assay to determine genotoxicity, and gel electrophoresis and flow cytometry to analyze DNA fragmentation and cell cycle distribution.

Chemically induced rat breast tumours are employed to evaluate in vivo activities.

For the most selective cytotoxin, 7(8)-bromo-2-hydroxyphenazine 5,10-dioxide (PDO1), exclusive hypoxic •OH production is evidenced, while for the unselective ones, •OH is produced in both conditions (normoxia and simulated hypoxia).

In normoxia (Caco-2 cells), PDO1 induces cell-cycle arrest and DNA fragmentation but does not significantly induce apoptosis neither at IC50 nor IC80.

No difference in the comet-assay scores are observed in normoxia and simulated hypoxia being the unselective 2-amino-7(8)-bromophenazine 5,10-dioxide (PDO2) the most genotoxic.

The in vivo efficacy with the absence of systemic toxicity of PDO1 and PDO2 is checked out.

Results from this study highlight the potential of PDOs as new therapeutics for cancer.

American Psychological Association (APA)

Lavaggi, María L.& Cabrera, Mauricio& Pintos, Cristina& Arredondo, Carolina& Pachón, Gisela& Rodríguez, Jorge…[et al.]. 2011. Novel Phenazine 5,10-Dioxides Release •OH in Simulated Hypoxia and Induce Reduction of Tumour Volume In Vivo. ISRN Pharmacology،Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-462705

Modern Language Association (MLA)

Lavaggi, María L.…[et al.]. Novel Phenazine 5,10-Dioxides Release •OH in Simulated Hypoxia and Induce Reduction of Tumour Volume In Vivo. ISRN Pharmacology No. 2011 (2011), pp.1-11.
https://search.emarefa.net/detail/BIM-462705

American Medical Association (AMA)

Lavaggi, María L.& Cabrera, Mauricio& Pintos, Cristina& Arredondo, Carolina& Pachón, Gisela& Rodríguez, Jorge…[et al.]. Novel Phenazine 5,10-Dioxides Release •OH in Simulated Hypoxia and Induce Reduction of Tumour Volume In Vivo. ISRN Pharmacology. 2011. Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-462705

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-462705