In Vivo Anti-Tumor Activity and Toxicological Evaluations of Perillaldehyde 8,9-Epoxide, a Derivative of Perillyl Alcohol

  • Int J Mol Sci. 2016 Jan 4;17(1):32. doi: 10.3390/ijms17010032.
Luciana Nalone Andrade  1 ,  Ricardo Guimarães Amaral  2 ,  Grace Anne Azevedo Dória  3 ,  Cecília Santos Fonseca  4 ,  Tayane Kayane Mariano da Silva  5 ,  Ricardo Luiz Cavalcante Albuquerque Júnior  6 ,  Sara Maria Thomazzi  7 ,  Lázaro Gomes do Nascimento  8 ,  Adriana Andrade Carvalho  9 ,  Damião Pergentino de Sousa  10
Affiliations
  • 1. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 2. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 3. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 4. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 5. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 6. Laboratório de Morfologia e Patologia Experimental, Instituto de Tecnologia e Pesquisa, CEP 49032-490, Aracaju, Sergipe CP 203, Brazil. [email protected].
  • 7. Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão, Sergipe CP 353, Brazil. [email protected].
  • 8. Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CEP 58051-970, João Pessoa, Paraíba CP 5009, Brazil. [email protected].
  • 9. Núcleo de Farmácia, Universidade Federal de Sergipe, CEP 49400-000, Lagarto, Sergipe CP 353, Brazil. [email protected].
  • 10. Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CEP 58051-970, João Pessoa, Paraíba CP 5009, Brazil. [email protected].
PMID: 26742032 DOI: 10.3390/ijms17010032
Abstract

Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(-)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the Animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol.

Keywords
anticancer; antitumor activity; essential oils; monoterpenes; natural products; p-menthanes; perillyl alcohol; sarcoma 180; toxicity.
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