Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells

The peripheral-type benzodiazepine receptor (PBR) expression and localizati on con elate with human breast cancer cell proliferation and aggressive phe notype expression. The standardized extract of Ginkgo biloba leaves (EGb 76 1) and isolated ginkgolide B (GKB) were shown to decrease PER mRNA expressi on in adrenal cells. We examined the effect of EGb 761 and GKB on PER expre ssion and cell proliferation in human breast cancel cells. EGb 761 and GKB decreased in a time- and dose-dependent manner PER expression and cell prol iferation in the highly aggressive, rich in PBR, human breast cancel cell l ine MDA-231 whereas they did not affect the proliferation of the non-aggres sive human breast cancer cell line MCF-7, which contains very low PER level s. This effect was reversible and nor due to the antioxidant properties of the compounds tested Using a human cDNA expression array we determined that EGb 761 treatment altered, in addition to PER, the expression of 36 gene p roducts involved in various pathways regulating cell proliferation. These i n vitro data were further validated in an in vivo model where EGb 761 and G KB significantly inhibited the nuclear PER expression and growth of MDA-231 cell xenografts in nude mice. Taken together, these data suggest that the manipulation of PBR expression could be used to cona ol tumor growth and th at EGb 761 and GKB, under the conditions used, exert cytostatic properties.