Triptolide simultaneously induces reactive oxygen species, inhibits NF-κB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines
Received 14 August 2009; received in revised form 14 October 2009; accepted 15 October 2009. published online 11 November 2009. Corrected Proof
Abstract
The in vitro chemosensitizing effect of triptolide (PG490) on the cytotoxicity of 5-fluorouracil (5-FU) was determined in three colorectal cancer (CRC) cell lines. PG490 alone was toxic to CRC cell lines (IC50s: 1.39–5.51nM). The cytotoxicity of 5-FU to CRC cell lines was 4–15-fold sensitized by combining use of low concentration of PG490. CI-isobologram indicated that the effect of PG490 plus 5-FU was synergistic. PG490 and 5-FU treatment induced activated caspase 3 and Bax expression and inhibited Bcl-2 expression. PG490 simultaneously induced generation of reactive oxygen species (ROS) and inhibited NF-κB transcriptional activity.
ABSTRACT
nM). The cytotoxicity of 5-FU to CRC cell lines was 4–15-fold sensitized by combining use of low concentration of PG490. CI-isobologram indicated that the effect of PG490 plus 5-FU was synergistic. PG490 and 5-FU treatment induced activated caspase 3 and Bax expression and inhibited Bcl-2 expression. PG490 simultaneously induced generation of reactive oxygen species (ROS) and inhibited NF-κB transcriptional activity.