Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells

Wei Jiunn Lee, Yun Ru Chen, Tsui Hwa Tseng

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Quercetin, a naturally occurring flavonoid abundant in fruits and vegetables, has been demonstrated as a multipotent bioflavonoid with great potential for the prevention and treatment of cancer. Apoptosis is thought to be an important response to most chemotherapeutic agents in leukemia cells. However, the underlying mechanism of induction of apoptosis by quercetin involving epigenetic regulation is poorly understood. In the present study, by evaluation of fragmentation of DNA, poly (ADP-ribose) polymerase (PARP) and procaspases, we found that quercetin was able to induce apoptosis of human leukemia HL-60 cells in a dose-dependent manner. Quercetin triggered the extrinsic apoptosis pathway through activation of caspase-8 and induction of Bid cleavage, Bax conformation change and cytochrome c release. Furthermore, quercetin induced Fas ligand (FasL) expression involving activation of the extracellular signal-regulated kinase (ERK) and Jun N-terminus kinase (JNK) signaling pathways. In addition to activation of c-Jun, quercetin increased histone H3 acetylation which resulted in the promotion of the expression of FasL. Quercetin exhibited potential for the activation of histone acetyltransferase (HAT) and the inhibition of histone deacetyltransferase (HADC), both of which contributed to histone acetylation. However, only the activation effect on HAT was associated with the ERK and JNK pathway. These results demonstrated that quercetin induced FasL-related apoptosis by transactivation through activation of c-jun/AP-1 and promotion of histone H3 acetylation in HL-60 cells.

Original languageEnglish
Pages (from-to)583-591
Number of pages9
JournalOncology Reports
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2011
Externally publishedYes

Fingerprint

Fas Ligand Protein
HL-60 Cells
Quercetin
Acetylation
Histones
Leukemia
Apoptosis
Histone Acetyltransferases
Extracellular Signal-Regulated MAP Kinases
Flavonoids
Phosphotransferases
Poly(ADP-ribose) Polymerases
Caspase 8
Transcription Factor AP-1
DNA Fragmentation
Cytochromes c
Epigenomics
Vegetables
Transcriptional Activation
Fruit

Keywords

  • Apoptosis
  • Fas ligand
  • Histone acetylation
  • Quercetin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells. / Lee, Wei Jiunn; Chen, Yun Ru; Tseng, Tsui Hwa.

In: Oncology Reports, Vol. 25, No. 2, 02.2011, p. 583-591.

Research output: Contribution to journalArticle

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