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Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer
Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A F Building, 02-097 Warsaw, Poland
Department III, Institute of Physical Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
* Author to whom correspondence should be addressed.
Received: 3 February 2011 / Accepted: 3 May 2011 / Published: 19 May 2011
(This article belongs to the Special Issue Prodrugs
Abstract: Aminolevulinic acid (ALA) is an endogenous metabolite normally formed in the mitochondria from succinyl-CoA and glycine. Conjugation of eight ALA molecules yields protoporphyrin IX (PpIX) and finally leads to formation of heme. Conversion of PpIX to its downstream substrates requires the activity of a rate-limiting enzyme ferrochelatase. When ALA is administered externally the abundantly produced PpIX cannot be quickly converted to its final product - heme by ferrochelatase and therefore accumulates within cells. Since PpIX is a potent photosensitizer this metabolic pathway can be exploited in photodynamic therapy (PDT). This is an already approved therapeutic strategy making ALA one of the most successful prodrugs used in cancer treatment.
Keywords: 5-aminolevulinic acid; photodynamic therapy; cancer; laser; singlet oxygen
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Wachowska, M.; Muchowicz, A.; Firczuk, M.; Gabrysiak, M.; Winiarska, M.; Wańczyk, M.; Bojarczuk, K.; Golab, J. Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer. Molecules 2011, 16, 4140-4164.
Wachowska M, Muchowicz A, Firczuk M, Gabrysiak M, Winiarska M, Wańczyk M, Bojarczuk K, Golab J. Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer. Molecules. 2011; 16(5):4140-4164.
Wachowska, Małgorzata; Muchowicz, Angelika; Firczuk, Małgorzata; Gabrysiak, Magdalena; Winiarska, Magdalena; Wańczyk, Małgorzata; Bojarczuk, Kamil; Golab, Jakub. 2011. "Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer." Molecules 16, no. 5: 4140-4164.