Effects of in vitro and in vivo treatment of monoterpene perillyl alcohol on proliferation and gene expression control of high grade gliomas

THESES

Effects of in vitro and in vivo treatment of monoterpene perillyl alcohol on proliferation and gene expression control of high grade gliomas (Abstract)^*. Dissertation. Rio da Janeiro, 2003.

Clóvis Orlando Pereira da Fonseca

^{Correspondence}

The search for new chemotherapeutic drugs has increased, especially for those that have a natural origin. Perillyl alcohol (POH), is a naturally occurring monoterpene, found in the essential oils of citrus fruits and other plants, with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. Standard treatment of anaplastic gliomas and glioblastoma multiforme consisting of surgical resection, radiation therapy and/or chemotherapy is rarely curative.

This study aimed to evaluate in vitro and in vivo effects of POH treatment, cell proliferation, changes in morphology, protein synthesis, and migration of distinct lineage of glioblastoma cells.

It was chosen in vitro culture systems and in vivo assays for assessing cellular migration. In vitro treatment of POH at concentrations of (v/v) 0.003%, 0.02%, 0.03%, 0.3%, 3% and 30%, consistently inhibited proliferation of murine C6 and human A172 and U87MG of glioblastoma cells.

In vitro treatment of POH at low concentrations 0.03% v/v and 0.3% v/v also produced marked changes in cell morphology and inhibited protein synthesis. Likewise in vitro assays with 0.3% v/v POH treatment for 15 minutes, initially caused marked alteration in membrane permeability and later (50 minutes) drastic changes in the cytoarchitecture of C6, U87MG and A172 cells. Furthermore, previous in vitro treatment of glioblastoma cells with 0.3% v/v and 0.03% v/v POH showed inhibition of cell migration and anti-metastatic activity in the in vivo model of the chick embryo with C6 cell line.

Such results indicate the chemotherapeutic action of POH by promoting cytotoxicity and arresting migration of murine and human glioblastoma cell lines.

Key words: glioblastoma chemotherapy, terpenes therapeutic use, gene expression, rat, in vitro, neovascularization.

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*

Efeito do tratamento in vitro e in vivo do monoterpeno álcool perílico no crescimento e controle da expressão gênica no glioma de alto grau (Resumo). Dissertação de Mestrado, Universidade Federal do Rio de Janeiro (Área: Neurologia). Orientadores: Abelardo de Queiroz-Campos Araújo; Thereza Quírico-Santos

Publication Dates

• Publication in this collection
  25 Apr 2006
• Date of issue
  Dec 2004