One of the most commonly investigated anticancer drug is 5-fluorouracil. It is employed clinically to treat solid tumors, e.g. colorectal, breast head and neck and several others. 5-fluorouracil is an antimetabolite which incorporates into DNA or RNA in place of thymine or uracil. It blocks the cell cycle and it is a proapoptotic agent. 5-fluorouracil has some adverse effects: stomatitis, bone marrow depression, diarrhea, nausea, vomiting, angina and cerebellar ataxia.

As it was described , chemopreventive agents may increase anticancer activity of chemotherapeutic agents and decrease their toxicity. Sulforaphane is an isothiocyanate naturally occurring in plants from the family Crucifera e.g.broccoli. It is widely known as a chemopreventive agent whose properties were proved in many cancer cell lines. Sulfaraphane induces the phase II enzymes and apoptosis, blocks the cell cycle and inhibits the phase I enzymes. Its multi-path activity provokes a question about possible interactions with anticancer drugs, among others 5-fluorouracil.

The aim of the study was to determine the type of interaction between  5-fluorouracil and sulforaphane in prostate cancer cell line PC-3. Antiproliferative effects of the substances were tested by the MTT assay. The type of interaction was established by the Chou and Talay method after sequential and co-administrative treatments. The mechanism of action was investigated with the flow cytometry assay: cytotoxic effect was examined with fluorescein diacetate/ propidum iodide staining and cytostatic effect was determined using the cell cycle distribution test. Additionally, the cell number after alone treatments and combination treatment was estimated.

The type of interaction depended on the cytotoxicity level. The antagonism was observed at the cytotoxicity level 0.75 after co-administrative treatment and at the cytotoxicity level 0.25 and 0.5 after sequential treatment. The synergic effect was shown at the cytotoxicity level 0.25 after co-administrative treatment. At the other cytotoxicity levels the additive effects were observed. Mechanism of antagonism was explained by the influence on different phases of a cell cycle by 5-fluorouracil and sulforaphane.The synergetic effect did not depend on cytotoxicity of the tested compounds or their cytostatic activity.

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