mRNA expression profile of a human cancer cell line in response to Ginkgo biloba extract: induction of antioxidant response and the Golgi system.
Supplementation of diets with plant extracts for health and prevention of degenerative diseases is popular. However the molecular basis of their therapeutic potentials are poorly defined. We hypothesized that in vitro assays that enable quantitative analysis of the gene expression profiles combined with targeted biochemical analysis can identify the potential effects of phytochemicals. The hypothesis was tested by application of GeneChips to define mRNA expressions of a human bladder cancer cell line incubated with a flavonoid containing extract of Ginkgo biloba leaves. The analysis of the transcriptional response revealed a net activation of transcription. Functional classification of the affected mRNAs showed the largest changes in the abundance of mRNAs for intracellular vesicular transport, mitochondria, transcription and antioxidants. The transcripts for hemeoxygenase-1, mitochondrial superoxide dismutase and the regulatory subunit of gamma-glutamyl-cysteinyl synthetase and their encoded proteins were elevated. The extract also increased intracellular glutathione, the transcripts for DNA repair and synthesis, and decreased 3H-thymidine incorporation. These results demonstrate that a flavonoid containing extract initiates an adaptive transcriptional response that augments the "antioxidant status" of the cells and inhibits DNA damage. These in vitro studies using GeneChips demonstrated a promising strategy for identifying nutritional supplement induced cellular responses that may have a role in counteracting chronic human diseases.
Gohil
K
K
Department of Molecular and Cell Biology, Lawrence Berkeley National Laboratory University of California, 94720, USA. kishor@socrates.berkeley.edu
Moy
R K
RK
Farzin
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S
Maguire
J J
JJ
Packer
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D000975:Antioxidants / Q000378:metabolism*; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D020441:Ginkgo biloba / Q000737:chemistry*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000032:analysis*; D013482:Superoxide Dismutase / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D000975:Antioxidants; D005419:Flavonoids; D008565:Membrane Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D004247:DNA; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione