Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 1, pp 45–52

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

  • 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
Original Article

DOI: 10.1007/s00280-010-1446-2

Cite this article as:
Magalhães, H.I.F., Bezerra, D.P., Cavalcanti, B.C. et al. Cancer Chemother Pharmacol (2011) 68: 45. doi:10.1007/s00280-010-1446-2

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.

Keywords

PhenstatinsTubulin inhibitorAntitumor activitySarcoma 180Toxicity

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hemerson Iury F. Magalhães
    • 1
  • Daniel P. Bezerra
    • 2
  • Bruno C. Cavalcanti
    • 1
  • Diego V. Wilke
    • 1
  • Rodrigo Rotta
    • 3
  • Dênis P. de Lima
    • 3
  • Adilson Beatriz
    • 3
  • Ana Paula N. N. Alves
    • 4
  • Flávio da S. Bitencourt
    • 1
  • Ingrid S. T. de Figueiredo
    • 1
  • Nylane M. N. Alencar
    • 1
  • Letícia V. Costa-Lotufo
    • 1
  • Manoel Odorico Moraes
    • 1
  • Claudia Pessoa
    • 1
  1. 1.Departamento de Fisiologia e Farmacologia, Faculdade de MedicinaUniversidade Federal do CearáFortalezaBrazil
  2. 2.Departamento de FisiologiaUniversidade Federal de SergipeSão CristóvãoBrazil
  3. 3.Departamento de Química (Laboratório LP4)Universidade Federal do Mato Grosso do SulCampo GrandeBrazil
  4. 4.Departamento de Clínica OdontológicaUniversidade Federal do CearáFortalezaBrazil