The nutrients or diet supplements can affected on orally administrated drugs absorption in intestine. Thus, it is extremely important to elucidate which of these food ingredients can impact drugs metabolism

Isothiocyanates (ITC) are found in vegetables from the family Cruciferous and they mainly occur in common consumed vegetables such as broccoli, cabbage, brussels sprouts, cauliflower etc. They are a group of compounds affecting the cells and modulating their metabolism in order to protect them against xenobiotics and other exogenous substances. They act by induction of phase 2 detoxification enzymes like glutathione S-transferases, NADPH: quinine oxidoreductase 1 (NQO1), etc. The gens encoding detoxifying and antioxidant proteins are regulated by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Under homeostatic conditions, Nrf2 is mainly sequestered in the cytoplasm by protein – Keap1. Various exogenous substances cause that Nrf2 is released from Keap1 protection and translocates to the nucleus, what results in transcriptional induction of phase 2 genes battery. But, it has already been shown that over-expression of Nrf2 enhances resistance of cancer cells to chemotherapeutic agents such as cispaltin, doxorubicin and etoposide.

In this study we evaluated the influence of naturally occurring ITC sulforaphane (SFN) on the activity of phase 2 enzymes, such as NQO1. The study was carried out in human intestinal Caco-2 cells, which are widely used as a model in drug development study including its permeability, transport and metabolism. In order to evaluate nontoxic doses of SFN we studied dose and time–dependent changes in viability of Caco-2 sells. We performed a MTT - cytotoxicity test, which is a quantitative colorimetric method for mammalian cell survival and cell proliferation. The NQO1 activity was determined by measuring the NADPH-dependent menadiol-mediated reduction of MTT. In order to study mechanism of NQO1 induction we also examined the time-dependent changes in the subcellular localization of Nrf-2 by immunostaining with anti-Nrf2 antibody and detection the results witch help of confocal microscope.

 Our results have shown dose–dependent changes in cell viability and time–dependent changes in NQO1, which indicates that SFN influence the 2 phase enzymes in Caco-2 cells. This in turn indicates that ITC present in nutrients or diet supplements can impact on bioavailability of drugs.

Badania finansowane przez Ministerstwo Nauki i Szkolnictwa Wyższego, projekt badawczy nr N405302236

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