Pyranocoumarin(+/-)-4'-O-acetyl-3'-O-angeloyl-cis-khellactone induces mitochondrial-dependent apoptosis in HL-60 cells

Planta medica
Wang-Fun FongMeng-Su Yang

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 pg/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-Xv. 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.

Citations

Dec 29, 2013·BioMed Research International·Parisa SarkhailPantea Sarkheil
Jan 1, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Ling HuangHui-Chang Bi
Mar 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wanghui JingQiang Fu
May 12, 2018·Molecular Nutrition & Food Research·Jing-Jing Zhu, Jian-Guo Jiang
Nov 11, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Taigang LiangQingshan Li
Apr 26, 2020·International Journal of Molecular Sciences·Chia-Liang LinChien-Min Chen

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