The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer HeLa cells.

Abstract	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer therapeutics. However, some tumor cells are resistant to TRAIL-induced apoptosis. Our previous studies have shown that luteolin, a naturally occurring flavonoid, induces the up-regulation of death receptor 5 (DR5), which is a receptor for TRAIL. Here, we show for the first time that luteolin synergistically acts with exogenous soluble recombinant human TRAIL to induce apoptosis in HeLa cells, but not in normal human peripheral blood mononuclear cells. The combined use of luteolin and TRAIL induced Bid cleavage and the activation of caspase-8. Also, human recombinant DR5/Fc chimera protein, caspase inhibitors, and DR5 siRNA efficiently reduced apoptosis induced by co-treatment with luteolin and TRAIL. These results raise the possibility that this combined treatment with luteolin and TRAIL might be promising as a new therapy against cancer.
Authors	Mano Horinaka, Tatsushi Yoshida, Takumi Shiraishi, Susumu Nakata, Miki Wakada, Ryoko Nakanishi, Hoyoku Nishino, Toshiyuki Sakai
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 333 Issue 3 Pg. 833-8 (Aug 05 2005) ISSN: 0006-291X [Print] United States
PMID	15963948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Apoptosis Regulatory Proteins BH3 Interacting Domain Death Agonist Protein BID protein, human Carrier Proteins Cysteine Proteinase Inhibitors Membrane Glycoproteins RNA, Small Interfering Recombinant Proteins TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Tumor Necrosis Factor-alpha CASP8 protein, human Caspase 8 Caspases Luteolin
Topics	Apoptosis (drug effects) Apoptosis Regulatory Proteins BH3 Interacting Domain Death Agonist Protein Carrier Proteins (metabolism) Caspase 8 Caspases (metabolism) Cysteine Proteinase Inhibitors (pharmacology) Enzyme Activation Female HeLa Cells Humans Luteolin (pharmacology) Membrane Glycoproteins (pharmacology) RNA, Small Interfering (metabolism) Recombinant Proteins (pharmacology) TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha (pharmacology) Uterine Cervical Neoplasms (pathology)

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