Epidemiological and biological evidence for protective effect of ginkgo biloba on ovarian cancer
Bin Ye, Dale Edwards, Ross S. Berkowitz, Samuel C. Mok, Daniel W. Cramer. Harvard Medical School, Boston, MA.
Anti-oxidants appear to exert apoptotic effects on a number of cancer cell lines and several categories of anti-oxidants have shown to be inversely correlated with cancer risk in epidemiological studies.
In the most recent phase of our population-based study of ovarian cancer involving eastern Massachusetts and New Hampshire, we asked about the use of several herbal anti-oxidants including the potent flavonoid anti-oxidant, Ginkgo Biloba.
Out of 668 cases with ovarian cancer, 11 (1.6%) said they had regularly used ginkgo at least weekly for a period of 6 months or longer, compared to 30 (4.2%) of controls who said they had used gingko regularly. This translated into a protective effect on ovarian cancer associated with the use of gingko, relative risk (rr) and (95% confidence limits) of RR=0.41 (0.20-0.84).
This risk was adjusted for site of study, age, oral contraceptive use, parity and Jewish ethnic background. To explore the biologic rational for this association, we next exposed two ovarian cancer cell lines OVCA433 and OVCA429 representing serous types of cancer to various gingko components.
Purified Quecenti, kaempferol, and standardized Ginkgo biloba extract powder were used to treat ovarian cancer cells. After treatment cells for 48 hours with either 100 ýM quercetin or kaempferol, we found that OVA433 cell growth was inhibited to levels representing about 70% of that observed in the controls.
Treatment with 10, 50, and 100 ýM of Ginkgo biloba extract strongly inhibited cell growth in a dose-dependent fashion to 57%, 37% and 23% of that observed in controls.
Conversely, treatment of OVCA429 ovarian cancer cells with quercetin and kaempferol at 50 and 100 ýM appeared to increase cell growth with both doses to 180% of that observed in control cells. Gingko biloba extracts at 10, 50, 100 ýM had no growth or inhibitory effect on OVCa429.
Western blot revealed that expression levels of P27 protein in OVCA433 cells were decreased by Ginkgo and quercetin treatment at concentration dependent manner. Our preliminary epidemiolgic data suggest that use of herbal forms of Gingko biloba may be inversely and significantly associated with ovarian cancer risk, while the cell line data is less clear.
Gingko biloba in its extracted form, rather that in the form of its key components, quercetin or kaempferol, appears to decrease cell growth in one ovarian cancer cell lines but not another. In the former cell line, the effect may be mediated through inhibition of a key cell cycle pathway of p27.
Abstract #3484 AACR 2005
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