Apoptosis

, 12:235

Comparison of the rapid pro-apoptotic effect of trans-ß-nitrostyrenes with delayed apoptosis induced by the standard agent 5-fluorouracil in colon cancer cells

  • Jens Martin Werner
  • Kurt Eger
  • Hans Jürgen Steinfelder
Article

DOI: 10.1007/s10495-006-0530-x

Cite this article as:
Werner, J., Eger, K. & Jürgen Steinfelder, H. Apoptosis (2007) 12: 235. doi:10.1007/s10495-006-0530-x

Abstract

Trans-ß-nitrostyrene (TBNS) has been reported to be a potent inhibitor of protein phosphatases PTB1 and PP2A and to display a pro-apoptotic effect even in multidrug resistant tumour cells. Here we compared the anti-tumour potential of TBNS with 5-fluorouracil (5-FU) as the standard chemotherapeutic agent for colorectal cancer in LoVo cells. Resistance to 5-FU based therapy might be a consequence of 5-FU’s delayed effect requiring long-term effective concentrations in the tumour tissue. Thus, alternatives like platin containing drugs with a more rapid effect have been introduced recently.

Compared to 5-FU TBNS displayed a faster cytotoxic and pro-apoptotic effect. A 50% decrease in viability was observed already after 8 h with TBNS while 5-FU displayed no significant effect before 48 h. DNA fragmentation and caspase-3 assays confirmed the more rapid apoptotic effect of TBNS. Since apoptosis affects individual cells these results about a rapidly induced apoptosis were further studied on a single cell level in microscopic assays of caspase-3 and caspase-8 activation.

Adducts of trans-ß-nitrostyrene displayed an anti-tumour effect comparable to TBNS which suggests the possibility of creating adducts with optimised tissue targeting. Finally, the calculation of a drug combination index displayed a synergistic effect for the combination of TBNS and 5-FU in Lovo as well as in HT-29 and HCT116 colon cancer cells.

Keywords

Trans-ß-nitrostyrene 5-Fluorouracil Drug-induced apoptosis Caspase-3 activation DNA fragmentation LoVo adenocarcinoma cells 

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Jens Martin Werner
    • 1
  • Kurt Eger
    • 2
  • Hans Jürgen Steinfelder
    • 1
  1. 1.Institute of Pharmacology & ToxicologyUniversity of GöttingenGöttingenGermany
  2. 2.Institute of PharmacyUniversity of LeipzigLeipzigGermany

Personalised recommendations