Triptolide simultaneously induces reactive oxygen species, inhibits NF-kappaB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines.
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 (IC(50)s: 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-kappaB transcriptional activity.
Xu
Bing
B
Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK.
Guo
Xiaoxia
X
Mathew
Sumi
S
Armesilla
Angel L
AL
Cassidy
James
J
Darling
John L
JL
Wang
Weiguang
W
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D015342:DNA Probes; D004224:Diterpenes / Q000494:pharmacology*; D054313:Drug Agonism; D004359:Drug Therapy, Combination; D004852:Epoxy Compounds / Q000494:pharmacology; D005472:Fluorouracil / Q000627:therapeutic use*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D015342:DNA Probes; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; C001899:triptolide; D008156:Luciferases; D005472:Fluorouracil