Original Article

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. MagalhãesAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
  • , Daniel P. BezerraAffiliated withDepartamento de Fisiologia, Universidade Federal de Sergipe Email author 
  • , Bruno C. CavalcantiAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
  • , Diego V. WilkeAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
  • , Rodrigo RottaAffiliated withDepartamento de Química (Laboratório LP4), Universidade Federal do Mato Grosso do Sul
  • , Dênis P. de LimaAffiliated withDepartamento de Química (Laboratório LP4), Universidade Federal do Mato Grosso do Sul
  • , Adilson BeatrizAffiliated withDepartamento de Química (Laboratório LP4), Universidade Federal do Mato Grosso do Sul
  • , Ana Paula N. N. AlvesAffiliated withDepartamento de Clínica Odontológica, Universidade Federal do Ceará
  • , Flávio da S. BitencourtAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
    • , Ingrid S. T. de FigueiredoAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
    • , Nylane M. N. AlencarAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
    • , Letícia V. Costa-LotufoAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
    • , Manoel Odorico MoraesAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará
    • , Claudia PessoaAffiliated withDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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

Phenstatins Tubulin inhibitor Antitumor activity Sarcoma 180 Toxicity