Differential enhancement of leukaemia cell differentiation without elevation of intracellular calcium by plant-derived sesquiterpene lactone compounds.

British Journal of Pharmacology
Seung Hyun KimT S Kim

Abstract

All-trans retinoic acid (ATRA) induces complete remission in a majority of acute promyelocytic leukaemia patients, but resistance of leukaemic cells to ATRA and its toxicity, such as hypercalcaemia, lead to a limitation of treatment. Therefore, combination therapies with differentiation-enhancing agents at non-toxic concentrations of ATRA may overcome its side effects. Here, we investigated the effect of plant-derived sesquiterpene lactone compounds and their underlying mechanisms in ATRA-induced differentiation of human leukaemia HL-60 cells. HL-60 cells were treated with four sesquiterpene lactones (helenalin, costunolide, parthenolide and sclareolide) and cell differentiation was determined by NBT reduction, Giemsa and cytofluorometric analyses. Signalling pathways were assessed by western blotting, gel-shift assay and kinase activity determinations and intracellular calcium levels were determined using a calcium-specific fluorescent probe. Helenalin, costunolide and parthenolide, but not sclareolide, increased ATRA-induced HL-60 cell differentiation into a granulocytic lineage. Signalling kinases PKC and ERK were involved in the ATRA-induced differentiation enhanced by all of the effective sesquiterpene lactones, but JNK an...Continue Reading

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Citations

Jul 17, 2012·Anti-cancer Drugs·Maria Regina Orofino KreugerKatharina D'Herde
May 20, 2015·International Journal of Molecular Sciences·Xuejing LinChangqing Su
Jul 24, 2013·Critical Reviews in Toxicology·M Helena R AmorimMargarida M S M Bastos
Aug 23, 2020·Pharmaceuticals·Malgorzata Sztiller-Sikorska, Malgorzata Czyz
Feb 28, 2018·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Sarita SaraswatiAbdelgalil M Abdelgadir
Aug 28, 2014·Cancer Prevention Research·Faya M MillimounoXiaomeng Li
Feb 27, 2009·Fitoterapia·Wen Jing Zhang, Lars Olof Björn
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