Transport and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde in Caco-2 cells

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Title
Transport and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde in Caco-2 cells
Author(s)
Kiho Lee; Song Kyu Park; Byoung-Mog Kwon; K J Kim; Hyung Eun Yu; J Ryu; Soo Jin Oh; K S Lee; Jong Soon KangC W Lee; M G Kwon; Hwan Mook Kim
Bibliographic Citation
Xenobiotica, vol. 39, no. 12, pp. 881-888
Publication Year
2009
Abstract
The transport and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde (BCA) was characterized in Caco-2 cells. BCA disappeared rapidly from the donor side without being transported to the receiver side during its absorptive transport across Caco-2 cells. Its metabolites 2'-hydroxycinnamaldehyde (HCA) and o-coumaric acid (OCA) were formed in both the donor and the receiver sides. HCA, in a separate study, also disappeared rapidly from the donor side, mostly being converted to its oxidative metabolite OCA during its absorptive transport across Caco-2 cells. OCA was transported rapidly in the absorptive direction across Caco-2 cells with a Papp of 25.4±1.0×10-6cm s-1 (mean±standard deviation (SD), n3). OCA was fully recovered from both the donor and the receiver side throughout the time-course of this study. Formation of HCA from BCA was inhibited almost completely by bis(p-nitrophenyl)phosphate (BNPP), a selective inhibitor of carboxylesterases (CES), and phenylmethylsulfonyl fluoride (PMSF), a broad specificity inhibitor of esterases in Caco-2 cells, suggesting that this hydrolytic biotransformation was likely mediated predominantly by CES. Conversion of HCA to OCA was inhibited significantly by isovanillin, a selective inhibitor of aldehyde oxidase (AO). Inhibitors for xanthine oxidase (XO) and aldehyde dehydrogenase (ALDH), which are known to be involved in the oxidation of aldehydes to carboxylic acids, did not have a significant effect on the biotransformation of HCA to OCA in Caco-2 cells. In summary, the present work demonstrates that BCA is hydrolysed rapidly to HCA, followed by subsequent oxidation to OCA, in Caco-2 cells. The results provide a mechanistic understanding of the poor absorption and low bioavailability of BCA after oral administration.
Keyword
2'-Benzoyloxycinnamaldehyde2'-hydroxycinnamaldehydeAnticancerAntitumourCaco-2MetabolismO-coumaric acidTransport
ISSN
0049-8254
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.3109/00498250903216000
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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