Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells.

Abstract

Luteolin, a naturally occurring flavonoid, induces apoptosis in various cancer cells. Little is known however concerning the underlying molecular mechanisms responsible for this activity. In this report, we reveal a novel mechanism by which luteolin-induced apoptosis occurs, and show for the first time that the apoptosis by luteolin is mediated through death receptor 5 (DR5) upregulation. Luteolin markedly induced the expression of DR5, along with Bcl-2-interacting domain cleavage and the activation of caspase-8, -10, -9 and -3. In addition, suppression of DR5 expression with siRNA efficiently reduced luteolin-induced caspase activation and apoptosis. Human recombinant DR5/Fc also inhibited luteolin-induced apoptosis. On the other hand, luteolin induced neither DR5 protein expression nor apoptosis in normal human peripheral blood mononuclear cells. These results suggest that DR5 induced by luteolin plays a role in luteolin-induced apoptosis, and raises the possibility that treatment with luteolin might be promising as a new therapy against cancer.

• Authors: Mano Horinaka, Tatsushi Yoshida, Takumi Shiraishi, Susumu Nakata, Miki Wakada, Ryoko Nakanishi, Hoyoku Nishino, Hiroshi Matsui, Toshiyuki Sakai
• Journal: Oncogene (Oncogene) Vol. 24 Issue 48 Pg. 7180-9 (Nov 03 2005) ISSN: 0950-9232 [Print] England
• PMID: 16007131 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Oncogene (2005) 24, 7180-7189. doi:10.1038/sj.onc.1208874; published online 11 July 2005.

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• Caspase Inhibitors
• Enzyme Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• RNA, Small Interfering
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor
• Recombinant Proteins
• TNFRSF10A protein, human
• TNFRSF10B protein, human
• Luciferases
• Luteolin

Topics

• Apoptosis (drug effects)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Blotting, Western
• Caspase Inhibitors
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• HeLa Cells
• Humans
• Luciferases (metabolism)
• Luteolin (pharmacology)
• Male
• Promoter Regions, Genetic
• Prostatic Neoplasms (pathology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor (genetics, metabolism)
• Recombinant Proteins (metabolism)
• Up-Regulation (drug effects)