ABC transporters and isothiocyanates: potential for pharmacokinetic diet–drug interactions

Abstract

Isothiocyanates, a class of anti-cancer agents, are derived from cruciferous vegetables such as broccoli, cabbage and watercress, and have demonstrated chemopreventive activity in a number of cancer models and epidemiologic studies. Due to public interest in cancer prevention and alternative therapies in cancer, the consumption of herbal supplements and vegetables containing these compounds is widespread and increasing. Isothiocyanates interact with ATP-binding cassette (ABC) efflux transporters such as P-glycoprotein, MRP1, MRP2 and BCRP, and may influence the pharmacokinetics of substrates of these transporters. This review discusses the pharmacokinetic properties of isothiocyanates, their interactions with ABC transporters, and presents some data describing the potential for isothiocyanate-mediated diet–drug interactions.

Glucosinolate hydrolysis and bioavailability of resulting isothiocyanates: Focus on glucoraphanin

“…Quercetin, naturally present in broccoli, and other flavonoids, are known to disrupt ABC transporters, including MRP2, enhancing SF absorption, by slowing secretion at the enterocyte (Alvarez et al, 2010). Separately, the up-regulation of ABC transporters/ multidrug resistance proteins by SF and ER is of concern for diet-drug interactions (Telang, Ji, & Morris, 2009). Whereas SF has been shown to upregulate GST and form a GSH conjugate in the enterocyte, to date, there were no indications of further metabolism of the GSH conjugate within the enterocyte (Petri et al, 2003).…”

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

“…As for pharmacokinetics of ITCs, PEITC has been studied extensively to characterize its properties. PEITC has high oral bioavailability and shows non linear elimination due at least partly to saturation of metabolism at doses 0.3-65 mg/kg body weight in rats (Telang et al, 2009). ITCs are consumed from foodstuff or food additives in man, and the absorption is suspected to be slower than that of gavage cases.…”

In Vivo Inhibition of BCRP/ABCG2 Mediated Transport of Nitrofurantoin by the Isoflavones Genistein and Daidzein: A Comparative Study in Bcrp1 −/− Mice

“…In this respect, it is important to consider the potential species differences with regard to flavonoid-BCRP interaction (20,21), and the fact that this interaction could depend on the substrate (28), as well as the effects that these compounds may have on other transporters and enzymes that may be important in the disposition of a drug (29). Mouse Bcrp1 shares only 81% amino acid identity with human BCRP (30), and even a single amino acid mutation at position 482 of BCRP was shown to significantly alter BCRP substrate and antagonist specificity (2).…”