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Antiprolfelative and cytotoxic effect of 5-fluorouracil and sulforaphane in Chinese hamster lung fibroblast cell line

Małgorzata Milczarek ,  Katarzyna Lubelska ,  Irena Misiewicz-Krzemińska ,  Katarzyna Wiktorska 

National Medicines Institut (NIL), Chełmska 30/34, Warsaw 00-725, Poland

Abstract

The 5-fluorouracil is the anti-cancer drug widely used for the treatment of colorectal, breast, head and neck, prostate, pancreas cancer. It causes a S phase block in cell cycle by inhibition of thymidylate synthase (TS). As many anticancer agents it’s responsible for the production of reactive oxygen species in cancer cells, which induces apoptosis.  

Sulforaphane is a naturally derived compound and is considered as a chemopreventive agent. It activates phase II enzymes in many types of cells and is known as indirect antioxidant. At higher doses it exhibits cytostatic and cytotoxic activity by influence on cell cycle and induction of apoptosis. Sulforaphane is widely used as dietary supplement, moreover it is widely present in diet since its main source are Brassica vegetable like broccoli and cabbage. Several studies have shown that sulforaphane can act synergistically with anti-cancer drugs in cancer cells. The combination treatment is more effective than either agent alone. The combination chemotheraphy can reduce doses of antitumor medicine and its toxicity. Only a few publications showed interactions between similar compounds in the normal cells. In this cases, antagonism is beneficial interaction and leads to a protective effect to normal cells.

The aim of our study was to evaluate if sulforaphane can attenuate toxic effect of cytostatic drug 5-fluorouracil in normal cells. We investigated: antipoliferative, cytotoxic effect of sulforaphane and 5-fluorouracil in normal cell line-Chinese hamster lung fibroblasts using the MTT assay,. The cell viability was studied using staining with FDA/PI and examined with confocal microscope. There were used the two schemes of administration: co-administration of 5-fluorouracil with sulforaphane and pre-treatment with sulforaphane with the subsequent treatment with 5-fluorouracil. The cells were also incubated with substances alone at the concentrations corresponding to the concentrations that were used in a combination.

It was observed that at low range of concentrations 5-fluorouracil is more cytotoxic than mixture or sulforaphane alone. This effect is stronger for the sequence administration than for co-administration. The FDA/PI staining showed that treatment did not caused death of cells since most of them were indicated as living cells.

 

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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna Lubelska
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-05 11:52
Revised:   2010-03-15 10:13