Isothiocyanate-drug interactions in the human adenocarcinoma cell line Caco-2.

Abstract

Isothiocyanates, among which alyssin is counted, are the compounds that have proved chemopreventive properties and the ability to induce the 2 and the 3 detoxification phase by affecting the transcription factor nuclear erythroid 2-related factor (Nrf2). Having a positive effect on the human body, these compounds are used as dietary supplements. Because of the observed increase in the consumption of dietary supplements taken along with the drugs routinely used in medical practice, this study examined the possibility of interactions between alyssin and drugs, which could have an impact on cell metabolism. We have determined the effects of the tested substances and their interactions on the expression and activity of the phase 2 genes, as well as on the drug transport, which could be influenced by affecting the expression of transport proteins that belong to the 3 phase of metabolism. It was also studied whether the transcription factor Nrf2 is responsible for the interactions that occurred. The results showed that the interactions between alyssin and the tested drugs strengthen or weaken the effect of the drugs given separately depending on the concentration of alyssin and the type of drug. Even though Nrf2 is involved in the interaction, it seems that it is not the only factor regulating the interactions between the tested medications.

• Authors: Katarzyna Lubelska, Irena Misiewicz-Krzemińska, Małgorzata Milczarek, Jolanta Krzysztoń-Russjan, Elżbieta Anuszewska, Karolina Modzelewska, Katarzyna Wiktorska
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 367 Issue 1-2 Pg. 19-29 (Aug 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 22527941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Anti-Arrhythmia Agents
• Cyclooxygenase Inhibitors
• Diuretics
• Isothiocyanates
• Multidrug Resistance-Associated Proteins
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Thiocyanates
• alyssin
• Furosemide
• Ketoprofen
• Verapamil
• NAD(P)H Dehydrogenase (Quinone)
• Glutathione Transferase
• glutathione S-transferase M1
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Active Transport, Cell Nucleus (drug effects)
• Adenocarcinoma
• Anti-Arrhythmia Agents (pharmacology)
• Caco-2 Cells
• Cell Survival (drug effects)
• Cyclooxygenase Inhibitors (pharmacology)
• Diuretics (pharmacology)
• Drug Interactions
• Furosemide (pharmacology)
• Gene Expression (drug effects)
• Glutathione Transferase (genetics, metabolism)
• Humans
• Inhibitory Concentration 50
• Isothiocyanates (pharmacology)
• Ketoprofen (pharmacology)
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Thiocyanates (pharmacology)
• Verapamil (pharmacology)