Studies on search for bioactive natural products targeting TRAIL signaling leading to tumor cell apoptosis

Med Res Rev. 2008 Sep;28(5):688-714. doi: 10.1002/med.20123.


Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells but not in normal cells and, hence, has been expected as a new anticancer strategy. During our studies on search for bioactive natural products from various natural resources such as plants and microorganisms, we recently identified several natural products which exhibited activities related to TRAIL signaling. Dimeric sesquiterpenoids isolated from Zingiberaceous plant, Curcuma parviflora, showed enhancement activity of gene expression of TRAIL-receptor and TRAIL-receptor protein level. Several new isoflavone natural products, named brandisianins, were isolated from Leguminosaeous plant, Millettia brandisiana, by our screening study targeting TRAIL-receptor expression enhancement activity. A dihydroflavonol (BB1) that was extracted from Compositaeous plant, Blumea balsamifera, and fuligocandin B, a new anthranilylproline-indole alkaloid isolated from myxomycete were found to exhibit reversal effect of TRAIL resistance activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Benz(a)Anthracenes / chemistry
  • Benz(a)Anthracenes / pharmacology
  • Caspases / metabolism
  • Drug Screening Assays, Antitumor
  • Humans
  • Isoflavones / pharmacology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Proline / analogs & derivatives
  • Proline / chemistry
  • Proline / pharmacology
  • Protein Kinases / metabolism
  • Receptors, Death Domain / agonists
  • Receptors, Death Domain / metabolism*
  • Sesquiterpenes / pharmacology
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / agonists
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Benz(a)Anthracenes
  • Isoflavones
  • Receptors, Death Domain
  • Sesquiterpenes
  • TNF-Related Apoptosis-Inducing Ligand
  • fuligocandin B
  • Proline
  • Protein Kinases
  • Caspases