The uptake of free and liposome-incorporated sclareol and its effect on
the growth of human cancer cell line HCT-116 was investigated. Recovery
of free and liposomal sclareol in cytosol, nuclei and crude membranes
was monitored over time. HCT-116 cells were incubated with 100 mu M of
free or liposomal sclareol up to 96 h. Intact cells were subjected to
subcellular fractionation in order to obtain highly purified fractions
of nuclei, cytosol, and crude membranes. Sclareol was extracted from
intact cells and from the subcellular fractions using the Bligh-Dyer
method and was measured by HPTLC/FID. The effect of sclareol on cell
growth was found time dependent. Free sclareol exhibited high toxicity,
while the liposomal sclareol showed reduced cytotoxicity but retained
the ability to reduce the cell growth rate. The uptake of sclareol by
the cells was faster and higher compared to that of its liposomal form.
The concentration of sclareol in the three subcellular fractions showed
that liposomal sclareol is incorporated in crude membranes and from
there it is released in cytosol and nuclei in a time dependent manner,
while free sclareol passes directly in the cytosol. These results
suggest that liposomal sclareol retains its growth inhibiting activity
while its cytotoxic action is diminished. These findings could be due to
the sustained delivery of sclareol to the different subcellular sites.
(c) 2006 Elsevier Masson SAS. All rights reserved
