<i>In Vitro</i> Effects of Paclitaxel and Cremophor EL on Human Riboflavin Transporter SLC52A2

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  • Hino Hitomi
    Translational Medicine Program, Research Institute, The Hospital for Sick Children
  • Yang Mingdong
    Translational Medicine Program, Research Institute, The Hospital for Sick Children
  • Dalvi Pooja
    Translational Medicine Program, Research Institute, The Hospital for Sick Children
  • Chen Tongtong
    Translational Medicine Program, Research Institute, The Hospital for Sick Children
  • Sun Linda
    Translational Medicine Program, Research Institute, The Hospital for Sick Children
  • Harper Patricia A.
    Department of Pharmacology and Toxicology, University of Toronto
  • Ito Shinya
    Translational Medicine Program, Research Institute, The Hospital for Sick Children Department of Pharmacology and Toxicology, University of Toronto Department of Paediatrics, The Hospital for Sick Children, University of Toronto

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  • In Vitro Effects of Paclitaxel and Cremophor EL on Human Riboflavin Transporter SLC52A2

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<p>Paclitaxel, a mitotic inhibitor with anti-cancer effects, is dissolved in Cremophor EL (CrEL). However, peripheral neuropathy is a known side effect. As one of the mechanisms of the neuropathy, mitochondrial dysfunction has been proposed, while peroxidation products are involved in the cause of CrEL-induced neurotoxicity. Riboflavin is an essential nutrient required for ATP production in mitochondria and has an antioxidant role as a coenzyme for glutathione. Therefore, riboflavin transporters might play a key role to mitigate neuropathy. However, it is unclear whether paclitaxel and CrEL affect these transporters. In this study, human riboflavin transporter SLC52A2 was used to analyze the effects of paclitaxel and CrEL. CrEL, but not paclitaxel, inhibited uptake of riboflavin in human embryonic kidney 293 cells transfected with the SLC52A2 expression vector, suggesting that altered riboflavin disposition may be involved in the pathogenesis of paclitaxel/CrEL toxicity.</p>

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