P-0184 - Selective, synergic and additive interaction types between 5-fluorouracil and 2-oxohexyl isothiocyanate after sequential treatment in colon cancer c...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Basic Science
Colon Cancer
Presenter Małgorzata Milczarek
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors M. Milczarek1, K. Wiktorska2, K. Lubelska2, L. Śliwka3, D. Matosiuk1, Z. Chilmonczyk2
  • 1Medical University, Faculty of Pharmacy with the Laboratory Medicine Division, Lublin/PL
  • 2National Medicines Institute, Warsaw/PL
  • 3Medical University, Faculty of Pharmacy with the Laboratory Medicine Division, Warsaw/PL

Abstract

Introduction

5-Fluorouracil is used to treat many types of cancers such as: breast, ovarian and gastrointestinal (e.g. colon or gastric) cancer. Until recently 5-fluorouracil was investigated as a candidate for prostate cancer therapy. The antitumor activity of 5-fluorouracil as a single agent is low (approximately 30%), hence it is used mainly in polytherapy. A few years ago a new idea was observed in scientific publications to enhance effectiveness of anticancer drugs through combined treatments with naturally occurring chemopreventive agents. Use of natural compounds increases efficacy of anticancer treatment and decreases toxicity in normal cells. One of the compounds is isothiocyanate-sulforaphane. It inhibits early stages of carcinogenesis and post-initiated stages of the process. In vitro studies show that it potentiates the activity of 5-fluorouracil, oxaliplatin and doxorubicin. Additionally, our previous studies indicate that sulforaphane acts antagonistically when combined with 5-fluorouracil in normal cell lines. The aim of this study was to investigate the type of interaction between 5-fluouracil and a more cytotoxic analogue of sulforaphane - 2-oxohexyl isothiocyanate - in two colon cancer and two prostate cancer cell lines.

Methods

The study was performed on cancer cell lines: prostate one (LNCaP and PC-3) and colon one (Caco-2and ht-29). The cytotoxic effects of single 5-fluorouracil or isothiocyanate treatments and their combination were evaluated by the MTT assay. There was used sequential schedule. The cells were treated with isothiocyanate and left for 24 hours and then they were subsequently incubated with 5-fluorouracil for 72 hours. The types of interaction were determined through the median effect analysis as described by Chou and Talalay and only when the combination inhibited cell proliferation in more than 50%.

Results

Synergic and additive types of interaction between isothiocyanate and 5-fluorouracil were observed in colon cancer cell lines. The cytotoxic effects of combination of 5-fluorouracil and 2 -oxohexyl isothiocyanate were stronger than the effects of single treatments. In one prostate cell line – LNCaP - there was observed antagonism and in the second prostate cell line - PC-3 – there were noticed additive effects of the tested compounds.

Conclusion

2 -oxohexyl isothiocyanate selectively potentiate5-fluorouracil anticancer activity in colon cancer cells lines.

Acknowledgment

The project was supported by the National Science Centre, Poland N/NZ5/02634. The publication was co-financed from the European Union funds by the European Social Fund.