International Journal of
Medicine and Medical Sciences

  • Abbreviation: Int. J. Med. Med. Sci.
  • Language: English
  • ISSN: 2006-9723
  • DOI: 10.5897/IJMMS
  • Start Year: 2009
  • Published Articles: 535

Full Length Research Paper

Preclinical biochemical studies using a novel 5-aminolevulinic acid ester derivative with superior properties for photodynamic therapy of tumors

Mohamed El-Far
  • Mohamed El-Far
  • Department of Chemistry, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.
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Mohamed Elshal
  • Mohamed Elshal
  • Molecular Biology Department, Genetic Engineering and Biotechnology Institute, Minoufiya University, Minoufiya, Egypt.
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Samir Bondock
  • Samir Bondock
  • Department of Chemistry, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.
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Manar Refaat
  • Manar Refaat
  • Department of Chemistry, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.
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  •  Accepted: 21 July 2009
  •  Published: 30 July 2009

Abstract

We have synthesized a novel 5-aminolevulinic acid (ALA) ester derivative from reacting ALA with β-citronellol and tested its potential for treatment of tumors by photodynamic therapy (PDT) in comparison to the widely used agents, ALA and Me-ALA (the methyl ester of ALA). The β-citronellol-ALA ester derivative was far superior to ALA in causing complete destruction of solid skin tumors after PDT treatment. Ex vivo PDT treatment of Ehrlich as cites carcinoma (EAC) cells indicated that the novel ester was effective in causing cell death and inhibition of cell growth, while flow cytometry studies revealed G0/G1 cell cycle arrest during the PDT-mediated response. Inoculation of healthy animals with EAC cell preparations extracted from tumor-bearing animals treated with various agents and then subjected to PDT treatment ex vivo revealed that the novel ester derivative was a significantly better agent than either ALA or Me-ALA at preventing or inhibiting growth of tumors in the inoculated animals. The findings suggest that the novel β-citronellol-ALA ester derivative offers a promising therapy for the treatment of apoptosis-reluctant tumors such as malignant tumors and may be superior to ALA or Me-ALA in PDT applications.

Key words: Cancer, PDT, ALA, β-citronellol-ALA ester derivative, flow cytometry, tumor apoptosis, ALA-PDT.