The coumarin psoralidin enhances anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Abstract

Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.

• Authors: Joanna Bronikowska, Ewelina Szliszka, Dagmara Jaworska, Zenon P Czuba, Wojciech Krol
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 17 Issue 6 Pg. 6449-64 (May 29 2012) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 22643355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzofurans
• Coumarins
• Receptors, Death Domain
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• psoralidin

Topics

• Antineoplastic Combined Chemotherapy Protocols (chemistry, pharmacology)
• Apoptosis (drug effects)
• Benzofurans (chemistry, pharmacology)
• Coumarins (chemistry, pharmacology)
• Drug Synergism
• Gene Expression (drug effects)
• HeLa Cells
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Receptors, Death Domain (genetics)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (genetics)
• TNF-Related Apoptosis-Inducing Ligand (chemistry, pharmacology)