Exp Mol Med.  2002 Dec;34(6):462-468.

Triptolide sensitizes lung cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by inhibition of NF-kappa B activation

• Lee KY
• Park JS
• Jee YK
• Rosen GD

Abstract

TNF-related apoptosis-inducing ligand (TRAIL/Apo- 2L), a newly identified member of the TNF family promotes apoptosis by binding to the transmembrane receptors (TRAIL-R1/DR4 and TRAIL-R2/ DR5). TRAIL known to activate NF-kappa B in number of tumor cells including A549 (wt p53) and NCI- H1299 (null p53) lung cancer cells exerts relatively selective cytotoxic affects to the human tumor cell lines without much effect on the normal cells. We set out to identify an agent that would sensitize lung cancer cells to TRAIL-induced apoptosis through inhibition of NF-kappa B activation. We found that triptolide, an oxygenated diterpene extracted and purified from the Chinese herb Tripterygium wilfordii sensitized A549 and NCI-H1299 cells to TRAIL-induced apoptosis through inhibition of NF-kappa B activation. Pretreatment with MG132 which is a well-known NF-kappa B inhibitor by blocking degradation of Ikappa B alpha also greatly sensitized lung cancer cells to TRAIL-induced apoptosis. Triptolide did not block DNA binding of NF-kappa B activated by TRAIL as in the case of TNF-alpha. It has been already proven that triptolide blocks transactivation of p65 which plays a key role in NF-kappa B activation. These observations suggest that triptolide may be a potentially useful drug to enhance TRAIL-induced tumor killing in lung cancer.

Keyword

antineoplastic agents; apoptosis; drug; Chinese herbal; lung neoplasms; NF-kappa B; tumor necrosis factor

MeSH Terms

Antineoplastic Agents/pharmacology
Apoptosis/*drug effects
Cell Line, Tumor
DNA/metabolism
Diterpenes/*pharmacology
Human
Lung Neoplasms/*metabolism/*pathology
Membrane Glycoproteins/*pharmacology
NF-kappa B/*antagonists & inhibitors/metabolism
Phenanthrenes/*pharmacology
Tumor Necrosis Factor/*pharmacology