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7beta-hydroxycholesterol blocked at C-3-OH inhibits growth of rat glioblastoma in vivo: comparison between 7beta-hydroxycholesteryl-3beta (ester)-oleate and 7beta-hydroxycholesteryl-3-beta-O (ether)-oleyl.

BACKGROUND
It was previously demonstrated that the 7beta-hydroxycholesteryl-3beta(ester)-oleate (7beta-ester) possesses antitumor properties against the experimental rat C6 glioblastoma. The effect of an analog of this molecule, 7beta-hydroxycholesterol-3beta-O(ether)-oleyl (7beta-ether), was investigated.


MATERIALS AND METHODS
Liposomes containing no oxysterol (control), 7beta-ether or 7beta-ester were injected into tumors induced by C6 cells in rat brain cortex. At defined times, the animals were sacrificed, the tumors stained with cresyl violet and their volumes measured by densitometry. Oxysterol clearance was assessed by quantification from lipid extraction of treated tumors.


RESULTS
The clearance of the new compound was slower than that of the 7beta-ester form. The 7beta-ether and 7beta-ester forms displayed similar antitumor activities against 3-day-old tumors. In contrast, the 7beta-ether form was more active on well-developed glioblastoma: 75 nmol inhibited tumor growth by 70% compared to controls, while the 7beta-ester had no effect under such conditions. The 7beta-ether form had a cytostatic rather than a cytotoxic effect. In addition, the composition of the liposomes did not affect the antitumor activity.


CONCLUSION
Only blockade of the C-3-OH group is required for the antitumor effect of this kind of oxysterol. It is suggested that the absence of "etherases" enhances the antitumor activity of this type of compound. Thus, an original therapeutic approach for glioblastoma treatment may be envisaged with such compounds.