Pyranocoumarin (±)-4′-O-acetyl-3′-O-angeloyl-cis- khellactone induces mitochondrial-dependent apoptosis in HL-60 cells

David W F FONG*, Jin Xia Zhang, Jimmy Yiu Cheong Wu, Anfernee K W TSE, Cheng Wang, Hong Yeung Cheung, Meng Su Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The pyranocoumarin (±)-4′-O-acetyl-3′-O-angeloyl-cis- khellactone (PC) isolated from Radix Peucedani (root of Peucedanum praeruptorum Dunn) showed a dose-dependent effect at 10 - 30 μg/mL on causing apoptotic DNA and nuclear fragmentations in HL-60 cells. After 24 h of PC treatment there were losses of mitochondrial membrane potential and cytochrome c. PC also increased total cellular and mitochondrial Bax protein, stimulated an increase in caspase-dependent Bcl-2 cleavage but showed no effect on Bcl-XL. These observations strongly suggest activation of the mitochondria apoptotic pathway. The pan-specific caspase inhibitor, ZVAD-fmk, abolished the PC-induced apoptosis, whereas the caspase-8 inhibitor IETD-fmk showed no effect, implying the involvement of the caspase 9 pathway. PC caused a 2 to 12 hour transient increase in phospho-ERK, and a 72 h-long activation of JNK. Pre-treatment with the MEK inhibitor PD98059, which suppresses ERK activation, paradoxically promoted PC-induced mitochondrial cytochrome c release, procaspase-3 and -8 cleavage, and enhanced apoptosis. Our results show that PC triggers mitochondria-mediated apoptosis in HL-60 cells, and the involvement of ERK and JNK signal pathways in the process.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalPlanta Medica
Volume70
Issue number6
DOIs
Publication statusPublished - Jun 2004

Scopus Subject Areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

User-Defined Keywords

  • 4′-O-acetyl-3′-O-angeloyl-khellactone
  • Apoptosis
  • Bax, Bcl-2
  • HL-60
  • Mitogen-activated protein kinases
  • Peucedanum praeruptonim
  • Umbelliferae

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