Different ways to induce apoptosis by fenretinide and all-trans-retinoic acid in human B lymphoma cells

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18 Citations (Scopus)

Abstract

All-trans-retinoic acid (ATRA) and its synthetic analog fenretinide (4HPR) are potent anticancer drugs. Only a few reports are available about the effects of retinoids on B lymphoma cells. In our study, non-Hodgkin lymphoma cells (HT58) were treated with ATRA and 4HPR. Both agents induced cell death time- and dose-dependentfy. Reactive oxygen species (ROS) production was elevated in 4HPR-treated cells, but not in ATRA-treated cells. The depolarization of the mitochondrial membrane occured earlier after ATRA than after 4HPR treament. Z-VAD-fmk, the general caspase inhibitor, decreased the DNA fragmentation in ATRA-treated cells, but simultaneously increased necrosis. However, z-VAD-fmk did not influence the DNA fragmentation in 4HPR-treated cells. Endonuclease G was released from the mitochondria during 4HPR treatment, which could be an inducer for caspase-independent DNA fragmentation. Our results suggest that natural (ATRA) and synthetic (4HPR) retinoids induce different apoptotic pathways in B lymphoma cells, which is particularly relevant for their potential use in leukemia treatment.

Original languageEnglish
Pages (from-to)4179-4185
Number of pages7
JournalAnticancer research
Volume25
Issue number6 B
Publication statusPublished - Nov 1 2005

Keywords

  • 4HPR
  • ATRA
  • Apoptosis
  • Lymphoma
  • Retinoids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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