Details

Autor(en) / Beteiligte

• Miura, Mai
• Ito, Kensuke
• Hayashi, Maiko
• Nakajima, Motowo
• Tanaka, Tohru
• Ogura, Shun-ichiro
• Pant, Aditya Bhushan

Titel

The Effect of 5-Aminolevulinic Acid on Cytochrome P450-Mediated Prodrug Activation

Ist Teil von

• PloS one, 2015-07, Vol.10 (7), p.e0131793

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Of late, numerous prodrugs are widely used for therapy. The hemeprotein cytochrome P450 (CYP) catalyzes the activation of prodrugs to form active metabolites. Therefore, the activation of CYP function might allow the use of lower doses of prodrugs and decrease toxicity. We hypothesized that the addition of 5-aminolevulinic acid (ALA), a precursor in the porphyrin biosynthetic pathway, enhances the synthesis of heme, leading to the up-regulation of CYP activity. To test this hypothesis, we treated a human gastric cancer cell line with ALA and determined the effect on CYP-dependent prodrug activation. For this purpose, we focused on the anticancer prodrug tegafur, which is converted to its active metabolite 5-fluorouracil (5-FU) mainly by CYP2A6. We show here that ALA increased CYP2A6-dependent tegafur activation, suggesting that ALA elevated CYP activity and potentiated the activation of the prodrug.