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01.07.2011 | Original Article

In vitro and in vivo antitumor effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone

verfasst von: Hemerson Iury F. Magalhães, Daniel P. Bezerra, Bruno C. Cavalcanti, Diego V. Wilke, Rodrigo Rotta, Dênis P. de Lima, Adilson Beatriz, Ana Paula N. N. Alves, Flávio da S. Bitencourt, Ingrid S. T. de Figueiredo, Nylane M. N. Alencar, Letícia V. Costa-Lotufo, Manoel Odorico Moraes, Claudia Pessoa

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2011

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Abstract

Purpose

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a phenstatin analog compound. PHT is a known tubulin inhibitor that has potent cytotoxic activity. In the present study, PHT was synthesized and its antitumor activity was determined using in vitro and in vivo experimental models.

Methods

The in vitro cytotoxic activity of the PHT was determined by the MTT assay. The antimitotic and hemolytic effects were determined based on the inhibition of sea urchin embryo development and lysis of mouse erythrocytes, respectively. In vivo antitumor activity was assessed in mice inoculated with sarcoma 180 cells.

Results

In vitro, PHT displayed cytotoxicity in tumor cell lines, showing IC₅₀ values in the nanomolar range. In addition, it inhibited sea urchin embryo development during all phases examined, first and third cleavage and blastula stage. However, PHT did not induce hemolysis using mouse erythrocytes, suggesting that the cytotoxicity of PHT does not involve membrane damage. The in vivo study demonstrated tumor inhibition rates of 30.9 and 48.2% for PHT at doses of 20 and 40 mg/kg, respectively. In addition, PHT was also able to increase the response elicited by 5-fluorouracil (5-FU) from 33.3 to 55.7%. The histopathological analysis of liver, kidney, and spleen showed that they were just moderately affected by PHT treatment. Neither enzymatic activity of transaminases nor urea levels were significantly affected. Hematological analysis showed leukopenia after 5-FU treatment, but this effect was prevented when 5-FU was combined with PHT.

Conclusions

In conclusion, PHT exhibited in vitro and in vivo antitumor effects without substantial toxicity.

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Titel: In vitro and in vivo antitumor effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone
verfasst von: Hemerson Iury F. Magalhães
Daniel P. Bezerra
Bruno C. Cavalcanti
Diego V. Wilke
Rodrigo Rotta
Dênis P. de Lima
Adilson Beatriz
Ana Paula N. N. Alves
Flávio da S. Bitencourt
Ingrid S. T. de Figueiredo
Nylane M. N. Alencar
Letícia V. Costa-Lotufo
Manoel Odorico Moraes
Claudia Pessoa
Publikationsdatum: 01.07.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2011
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1446-2

Springer Medizin

In vitro and in vivo antitumor effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone