Enhancement of 1α,25‐dihydroxyvitamin D₃‐induced differentiation of human leukaemia HL‐60 cells into monocytes by parthenolide via inhibition of NF‐κB activity

Abstract

1 Transcription factors such as NF-kB provide powerful targets for drugs to use in the treatment of cancer. In this report parthenolide (PT), a sesquiterpene lactone of herbal remedies such as feverfew (Tanacetum parthenium) with NF-kB inhibitory activity, markedly increased the degree of human leukaemia HL-60 cell dierentiation when simultaneously combined with 5 nM 1a,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ). PT by itself did not induce HL-60 cell dierentiation. 2 Cyto¯uorometric analysis indicated that PT stimulated 1,25-(OH) 2 D 3 -induced dierentiation of HL-60 cells predominantly into monocytes. 3 Pretreatment of HL-60 cells with PT before the 1,25-(OH) 2 D 3 addition also potentiated the 1,25-(OH) 2 D 3 -induced HL-60 cell dierentiation in both a dose-and a time-dependent manner, in which the enhanced levels of cell dierentiation closely correlated with the inhibitory levels of NF-kB binding activity by PT. 4 In contrast, santonin, a sesquiterpene lactone without an inhibitory activity of NF-kB binding to the kB sites, did not enhance the 1,25-(OH) 2 D 3 -induced HL-60 cell dierentiation. 5 In transfection experiments, PT enhanced 1,25-(OH) 2 D 3 -induced VDRE-dependent promoter activity. Furthermore, PT restored 1,25-(OH) 2 D 3 -induced VDRE-dependent promoter activity inhibited by TNF-a, an activator of NF-kB signalling pathway. 6 These results indicate that PT strongly potentiates the 1,25-(OH) 2 D 3 -induced HL-60 cell dierentiation into monocytes via the inhibition of NF-kB activity and provide evidence that inhibition of NF-kB activation can be a pre-requisite to the ecient entry of promyelocytic leukaemia cells into a dierentiation pathway.

Planarians in pharmacology: parthenolide is a specific behavioral antagonist of cocaine in the planarian Girardia tigrina

“…1B) is the active component of the feverfew plant (T. parthenium), used to treat migraines. This compound has several known biochemical effects, including the inhibition of serotonin type II receptors (Weber et al, 1997) and the enhancement of NF-kB transcription factor function (Kang et al, 2002). Also, parthenolide displays anti-inflammatory effects and inhibits Ikappa-B kinases (Kwok et al, 2001).…”

The germacranolide sesquiterpene lactone neurolenin B of the medicinal plant Neurolaena lobata (L.) R.Br. ex Cass inhibits NPM/ALK-driven cell expansion and NF-κB-driven tumour intravasation

“…Nevertheless, it is evident that tumour intravasation through the LEC barrier depends in part on NF-κB activity (Viola et al 2013a;Vonach et al 2011) and that neurolenin B, such as lobatin B, inhibited CCID formation due to NF-κB inhibition (Kiss et al 2015). Furthermore, the attenuation of HL60 leukaemia cell growth was most likely due to NF-κB inhibition (Kang et al 2002) and also the use of N. lobata decoctions as an antiinflammatory remedy (Arvigo and Balick 1998) is certainly based on this property.…”

“…6b). Thus, also the proliferation of leukaemia cells that are not harbouring the NPM/ALK translocation was affected by neurolenin B. Sesquiterpene lactones are potent inhibitors of NF-κB (Kwok et al 2001) and the permanently over-activated NF-κB pathway in HL60 cells (Kang et al 2002) may have been a target of neurolenin B thereby reducing their expansion. This was a likely mechanism of neurolenin B exhibiting anti-leukaemia/lymphoma specificity.…”

A20 gene expression is regulated by TNF, Vitamin D and androgen in prostate cancer cells

“…It was shown that A20 expression was regulated at the transcriptional level through B elements in the promoter region of the A20 gene [24]. The ability of Vitamin D to regulate the activity of NF-B has been demonstrated in human fibroblasts [25], human leukaemia [26][27][28] and insulinoma cells [29]. The effects of Vitamin D varied and appear to be cell specific.…”