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## The mechanism of chemopreventive action of isothiocyanates in Caco-2 colon cancer cells

### Ilona Zbroińska

#### Abstract

The continuous increase in the incidence of cancer, including cancer of the colon, stimulates the search for new treatments and prevention. Special interest is the chemoprevention, based on the use of natural, non-toxic compounds for the prevention of cancer and inhibition of tumor growth. Isothiocyanates are a group of widely described compounds which possess chemopreventive properties. Chemopreventive properties of isothiocyanates are based primarily on improving the detoxification of cells through the induction of II and III biotransformation phase enzymes. The first step was to define cytotoxicity of isothiocyanates in colon cancer cells Caco-2. Then the effect of isothiocyanates on the activity of phase III biotransformation transport proteins – MRP and Pgp and their ability to induce translocation factor Nrf2 were investigated. Isothiocyanates cytotoxicity assay, using MTT, allowed the determination of non-toxic concentrations of the compounds, as well as a comparison of the toxicity of the tested compounds. In order to determine the effects of isothiocyanates on phase III protein activity – MRP and Pgp – test with calcein-AM and suitable inhibitors was performed. The rating of Nrf2 translocation from the cytoplasm to the nucleus was carried out by immunofluorescence staining. The results suggest that isothiocyanates having methylsulphinyl group – sulforaphane and alyssin – show substantially less cytotoxicity as compared to those with acetyl group – 2-oxohexyl and 2-oxoheptyl isothiocyanates. Study of the effect of isothiocyanates on the translocation of Nrf2 and activity of Pgp, MRP proves that by influencing factor Nrf2, they can induce the activity of MRP. Isothiocyanates can also influence the activity of Pgp but the mechanism of this effect, due to the lack of sequence ARE, is not known. MRP activity increases to a greater extent after incubation with isothiocyanates having methylsulphinyl group, whereas isothiocyanates with an acetyl group, to a lesser extent, induce the activity of the protein. In the case of Pgp, effect on activity depend on the length of the methylene chain. The derivatives of shorter carbonic chain result in a reduction of activity, while derivatives with a higher number of carbon atoms in the chain – growth activity. As indicated by the results, a number of chemopreventive properties of isothiocyanates can make a significant contribution to the defense of the organaism against the formation and development of cancer.
Record ID
WUTc88eeca7335e4c71b1a6108ae4411ca1
Diploma type
Master of Science
Author
Ilona Zbroińska Ilona Zbroińska,, Undefined Affiliation
Title in Polish
Mechanizm chemoprewentywnego działania izotiocyjanianów w nowotworowych komórkach okrężnicy Caco-2
Supervisor
Ilona Grabowska-Jadach (FC/CMB) Ilona Grabowska-Jadach,, Chair of Medical Biotechnology (FC/CMB)Faculty of Chemistry (FC)
Certifying unit
Faculty of Chemistry (FC)
Affiliation unit
Department Of Microbioanalytics (FC/CMB)
Study subject / specialization
, Biotechnologia Chemiczna - Leki i Kosmetyki
Language
(pl) Polish
Status
Finished
Defense Date
25-09-2012
Issue date (year)
2012
Keywords in Polish
-
Keywords in English
-
Abstract in Polish
urn:pw-repo:WUTc88eeca7335e4c71b1a6108ae4411ca1