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 localization correlate with human breast cancer cell proliferation and aggressive phenotype expression. The standardized extract of Ginkgo biloba leaves (EGb 761) and isolated ginkgolide B (GKB) were shown to decrease PBR mRNA expression in adrenal cells. We examined the effect of EGb 761 and GKB on PBR expression and cell proliferation in human breast cancer cells. EGb 761 and GKB decreased in a time- and dose-dependent manner PBR expression and cell proliferation in the highly aggressive, rich in PBR, human breast cancer cell line MDA-231 whereas they did not affect the proliferation of the non-aggressive human breast cancer cell line MCF-7, which contains very low PBR levels. This effect was reversible and not 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 PBR, the expression of 36 gene products involved in various pathways regulating cell proliferation. These in vitro data were further validated in an in vivo model where EGb 761 and GKB significantly inhibited the nuclear PBR 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 control tumor growth and that EGb 761 and GKB, under the conditions used, exert cytostatic properties.
Papadopoulos
V
V
Department of Cell Biology and Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA. papadopv@gunet.georgetown.edu
Kapsis
A
A
Li
H
H
Amri
H
H
Hardwick
M
M
Culty
M
M
Kasprzyk
P G
PG
Carlson
M
M
Moreau
J P
JP
Drieu
K
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004224:Diterpenes; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D020441:Ginkgo biloba; D046934:Ginkgolides; D006801:Humans; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008024:Ligands; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts; D010946:Plants, Medicinal; D012333:RNA, Messenger; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D000096983:Ginkgo Extract
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004224:Diterpenes; D005419:Flavonoids; D046934:Ginkgolides; D007783:Lactones; D008024:Ligands; D010936:Plant Extracts; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C045856:ginkgolide B