Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.

• Authors: Ewelina Szliszka, Dagmara Jaworska, Małgorzata Ksek, Zenon P Czuba, Wojciech Król
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 13 Issue 11 Pg. 15343-59 (Nov 20 2012) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 23203129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Recombinant Proteins
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10B protein, human
• Chalcone

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Chalcone (pharmacology, toxicity)
• Drug Synergism
• HeLa Cells
• Humans
• Neoplasms (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (antagonists & inhibitors)
• Recombinant Proteins (metabolism, pharmacology)
• TNF-Related Apoptosis-Inducing Ligand (metabolism, pharmacology, toxicity)