Antibody-microarray data showing Ginkgolide induces multiple anti-cancer targets/pathways in BRCA1 ovarian epithelial cells

A120

Background: Women who carry BRCA1/2 mutations have a higher risk of developing ovarian cancers. Options to reduce this risk are largely limited to prophylactic surgery. Our previous epidemiological and biological studies showed that use of the herbal remedy of Ginkgo biloba, may reduce the risk for non-mucinous and largely non-familial ovarian cancer. Here we explore whether Ginkgo biloba might also be effective in reducing the risk for BRCA1 associated ovarian cancer through the use of cell lines and novel antibody microarray technology.
 >Methods: A human ovarian surface epithelial cell line (HOSE636) was developed from a BRCA1 mutant carrier who had prophylactic surgery but no cancer found. Ginkgolide B (100μM) plus DMSO-PBS buffer or DMSO-PBS buffer alone were used for continuous treatment for 7 days. Protein lysates from the treated and non-treated cells were applied to antibody microarrays, which contain 500 monoclonal antibodies for relevant cancer protein targets, to determine which proteins might be up or down- regulated by the ginkgolide treatment. Differential protein expression in the treated and untreated cells were analyzed and classified using a heat-map display. Anti-cancer activities and the associated networking pathways in the BRCA1 treated and untreated ovarian epithelial cells were analyzed using the Pathway Studio software.
 >Results: The HOSE 636 cell demonstrated two truncated BRCA1 protein fragments rather than the intact protein. After ginkgolide B treatment, 28 proteins were shown to be consistently up regulated (1.5 to 15.5-fold), and 22 proteins were down regulated (1.5 to 28.3-fold). Our preliminary studies showed that 25 of the 28 up-regulated proteins were associated with anti-tumor activities such as P53, while all of the ginkgolide down-regulated proteins in BRCA1 ovarian epithelial cells were positively linked to cancer transformation and metastasis such as paxillin and β-catenin. Systematic pathway analysis indicated that multiple mechanisms and signal pathways may result in anti-cancer activities in BRCA1 mutant cells when treated with Ginkgolide B. These pathways include cell proliferation (i.e. PU.1, paxillin, β-catenin), tumor suppression (i.e. P53), invasion (Fibronectin), DNA damage signaling and repair (ERCC1, XPA, SRPK1). Conclusion: Our study demonstrated that ginkgolide B found in the herbal Ginkgo biloba has anti-cancer activities in BRCA1 mutant ovarian surface epithelial cells. Further studies of the use of Ginkgo as a chemopreventive agent in women who carry BRCA mutations are justified.