The isothiocyanate produced from glucomoringin inhibits NF-kB and reduces myeloma growth in nude mice in vivo

Abstract

Glucosinolates (GLs), natural compounds extracted from Brassicaceae and precursors of isothiocyanates (ITCs), have been studied in the last decades mostly due to their chemopreventive activity and, more recently, for their potential use as novel chemotherapeutics. The aim of the present study was to investigate the in vitro and in vivo activity of glucomoringin (GMG), an uncommon member of the GLs family, and to compare it with glucoraphanin (GRA), one of the most studied GL. We have evaluated the potency of both compounds in inducing cell death, cell cycle perturbations, apoptosis, NF-kB inhibition and GST-pi activity in human carcinoma cells with different GST-pi contents as well as in human multiple myeloma and leukaemia cell lines. GMG-derived ITC (GMG-ITC) showed to be more effective compared to GRA-derived ITC (Sulforaphane), especially in inhibiting NF-kB activity and inducing apoptosis through a caspase-dependent pathway; these effects were more pronounced in myeloma cells, in which we could also observe a long lasting growth inhibitory effect, probably due to NF-kB inhibition, which is considered essential for myeloma cell survival. Both GLs were able to induce cell death in the muM range in all tested cell lines but caused cell cycle perturbations only in myeloma cells; they were also able to modulate the GST/GSH pathway by causing a 3-fold increase in GST-pi activity in MCF7 cells. In vivo study showed that pure GMG-ITC was only slightly active in a carcinoma mice model, whereas it had significant antitumoral activity in a myeloma model, causing little toxicity.

Status and utilisation of Moringa oleifera Lam: A review

“…In addition, Moringa was found to have a group of unique compounds containing sugar and rhamnose, which are uncommon sugar modified glucosinolates (Fahey et al, 2001;Fahey, 2005). These compounds were reported to demonstrate certain chemopreventive activity, by inducing apoptosis (Brunelli et al, 2010). The species has a particularly high level of oleic acid (70%), making it a great moisturiser, as well as a potentially healthy source of fat in the diet (other vegetable oils normally contain only about 40% oleic acid).…”

Moringa oleifera: An underutilized tree in Nigeria with amazing versatility: A review

“…In addition, the Moringa was found to have a group of unique compounds containing sugar and rhamnose, which are uncommon sugarmodified glucosinolates (Fahey et al, 2001;Fahey, 2005;Amaglo et al, 2010). These compounds were reported to demonstrate certain chemopreventive activity, by inducing apoptosis (Brunelli et al, 2010).…”

Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro

“…For example, compound 5 was a stronger inhibitor of NF-κB expression and myeloma growth in nude mice than SF (Brunelli et al, 2010). Compounds 5-8 also reduced NO formation at low micromolar concentrations in macrophages (Cheenpracha et al, 2010).…”

“…The moringa ITCs are solid and relatively stable compounds at room temperature, in contrast to volatile ITCs from crucifers that are mostly viscous liquids. The retained rhamnose sugar moiety found in moringa ITCs is extremely unique in nature and likely responsible for their high stability and solid appearance (Brunelli et al, 2010). Previous research with moringa extracts has predominantly utilized commercially available dried leaf powder for experimentation.…”