Application Notes:
N-Dodecanoyl-NBD-L-threo-dihydrosphingosine is a synthetic dihydroceramide analog containing the 7-(4-nitrobenzo-2-
oxa-1,3-diazole) (NBD) fluorescent group. NBD has been shown to have only a small influence on lipid adsorption into cells
and cellular membranes in many applications. This fluorescent analog of L-threo-dihydroceramide is comparable to C12:0-
L-threo-dihydroceramide in some biological functions. Safingol is a fully saturated, non-natural analog of sphingosine that
has anticancer properties and is being investigated for its potential as an antitumor therapy. It has been shown to inhibit both
protein kinase C (PKC) and sphingosine kinase. Safingol competitively interacts at the regulatory phorbol-binding domain of
PKC, a kinase involved in tumorigenesis. Safingol has been shown to potentiate the effect of doxorubicin (DOX) in tumorbearing
animals.1 It has been reported that safingol is able to increase the activity of DOX and other chemotherapeutic
agents, including mitomycin C, by generating the pro-apoptotic second messenger ceramide, even in tumor cell lines that
were resistant to chemotherapy due to mutations.2 However, a study has recently claimed that safingol induces cell death of
an exclusively autophagic character and lacking any of the hallmarks of apoptosis.3 Safingol inhibited the reactive oxygen
intermediates (ROI) released from isolated neutrophils and phorbol ester-induced edema and neutrophil influx. Safingol also
demonstrates anti-inflammatory activity. Safingol, like the natural D-erythro-sphinganine, is used as a biosynthetic precursor
for all complex sphingolipids althogh the metabolism of the natural and the non-natural compounds are different.4
References:
1. Darges, et al. “Inhibition of leukotriene B4 (LTB4) in human neutrophils by L-threo-dihydrosphingosine” Adv. Exp. Med. Biol, Vol. 400A pp. 387-392,
1997
2. G. Schwartz, et al. “A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin”
Clin. Cancer Res, Vol. 3 pp. 537-543, 1997
3. J. Coward et al. “Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway”
Autophagy Vol. 5(2) pp.184-193, 2009
4. M. Dragusin et al. “Metabolism of the unnatural anticancer lipid safingol,L-threo-dihydrosphingosine, in cultured cells” Vol. 44 pp. 1772, 2003