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

Mano Horinaka, Tatsushi Yoshida, Takumi Shiraishi, Susumu Nakata, Miki Wakada, Ryoko Nakanishi, Hoyoku Nishino, Toshiyuki Sakai

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)833-838
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Aug 5 2005
Externally publishedYes


  • Apoptosis
  • Cancer
  • Caspase
  • Combination
  • DR5
  • Flavonoid
  • Luteolin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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