Pyranocoumarin (±)-4′-O-acetyl-3′-O-angeloyl-cis- khellactone induces mitochondrial-dependent apoptosis in HL-60 cells
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
Author(s)
Detail(s)
Original language | English |
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Pages (from-to) | 489-495 |
Journal / Publication | Planta Medica |
Volume | 70 |
Issue number | 6 |
Publication status | Published - Jun 2004 |
Link(s)
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.
In: Planta Medica, Vol. 70, No. 6, 06.2004, p. 489-495.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review