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

Masami Ishibashi1, Takashi Ohtsuki

  • 1Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.

Medicinal Research Reviews
|February 15, 2008
PubMed

Insights

Natural products enhance Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL) signaling. Compounds from Curcuma parviflora and Millettia brandisiana boost TRAIL-receptor expression, while others reverse TRAIL resistance in cancer cells.

Area of Science:

  • Natural Product Chemistry
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells, presenting a promising anticancer strategy.
  • Identifying natural products that modulate TRAIL signaling is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To discover and characterize natural products with TRAIL signaling modulation activities.
  • To investigate the potential of these natural products as anticancer agents by targeting TRAIL pathways.

Main Methods:

  • Isolation and structural elucidation of bioactive compounds from Zingiberaceae (Curcuma parviflora), Leguminosae (Millettia brandisiana), Compositae (Blumea balsamifera), and myxomycetes.
  • Assays to evaluate enhancement of TRAIL-receptor gene expression and protein levels.
  • Assessment of reversal effects on TRAIL resistance in cancer cells.

Main Results:

  • Dimeric sesquiterpenoids from Curcuma parviflora enhanced TRAIL-receptor gene expression and protein levels.
  • New isoflavones, brandisianins, from Millettia brandisiana also showed TRAIL-receptor expression enhancement.
  • A dihydroflavonol (BB1) and fuligocandin B reversed TRAIL resistance, indicating potential to overcome treatment unresponsiveness.

Conclusions:

  • Several natural products derived from diverse botanical and microbial sources exhibit significant modulation of TRAIL signaling pathways.
  • These findings highlight the therapeutic potential of natural products in cancer treatment by enhancing TRAIL-induced apoptosis and overcoming resistance.

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