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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Wang-Fun Fong
  • Jin-Xia Zhang
  • Jimmy Yiu-Cheong Wu
  • Kai-Wing Tse
  • Cheng Wang
  • Hong-Yeung Cheung

Detail(s)

Original languageEnglish
Pages (from-to)489-495
Journal / PublicationPlanta Medica
Volume70
Issue number6
Publication statusPublished - Jun 2004

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.

Research Area(s)

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

Citation Format(s)

Pyranocoumarin (±)-4′-O-acetyl-3′-O-angeloyl-cis- khellactone induces mitochondrial-dependent apoptosis in HL-60 cells. / Fong, Wang-Fun; Zhang, Jin-Xia; Wu, Jimmy Yiu-Cheong et al.
In: Planta Medica, Vol. 70, No. 6, 06.2004, p. 489-495.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review