Mechanisms of fenretinide-induced apoptosis

Apoptosis. 2006 Oct;11(10):1677-94. doi: 10.1007/s10495-006-9289-3.


Fenretinide, a synthetic retinoid, has emerged as a promising anticancer agent based on numerous in vitro and animal studies, as well as chemoprevention clinical trials. In vitro observations suggest that the anticancer activity of fenretinide may arise from its ability to induce apoptosis in tumor cells. Diverse signaling molecules including reactive oxygen species, ceramide, and ganglioside GD3 can mediate apoptosis induction by fenretinide in transformed, premalignant, and malignant cells. In many cell types, these signaling intermediates appear to be induced by mechanisms that are independent of retinoic acid receptor activation, and ultimately initiate the intrinsic or mitochondrial-mediated pathway of cell elimination. Numerous investigations conducted during the past 10 years have discovered a great deal about the apoptogenic activity of fenretinide. In this review we explore the mechanisms associated with fenretinide-induced apoptosis and highlight certain mechanistic underpinnings of fenretinide-induced cell death that remain poorly understood and thus warrant further characterization.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Fenretinide / pharmacology*
  • Humans
  • Matrix Metalloproteinases / physiology
  • Models, Biological
  • Neoplasms / drug therapy
  • Neoplasms / prevention & control
  • Preventive Medicine / methods
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Protein Denaturation / physiology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Tretinoin / analogs & derivatives


  • Antineoplastic Agents
  • Protective Agents
  • Reactive Oxygen Species
  • Fenretinide
  • Tretinoin
  • Matrix Metalloproteinases