Inhibitory effects of Ginkgo biloba extract on aromatase activity and tumor suppression in aromatase xenograft model

Aromatase is a responsible enzyme for the biosynthesis of estrogen, and Aromatase Inhibitor (AI) became a first line therapy in postmenopausal breast cancer patients. Ginkgo biloba extract (GBE) is the most popular natural extract, and widely used in various symptoms, such as cardiovascular, renal, respiratory and central nervous system disorders. In this study, we showed that GBE significantly inhibited aromatase activity in aromatase over-expressed MCF-7 (MCF-7 AROM) cells and reduced estrogen-dependent tumor growth in aromatase xenograft model. GBE (100 – 1,000 µg/ml) significantly inhibited aromatase activity in directly and indirectly and its inhibition was accompanied with reduced aromatase mRNA expression and E2 synthesis. 1,000 µg/ml of EGB 761 directly inhibited aromatase activity to 45.12 ± 0.57% and indirectly inhibited aromatase activity to 34.21 ± 5.16% compare to vehicle control group. Major components of GBE, kaempferol (10 – 100µM) and quercetin (10 – 100µM) were tested for aromatase inhibition, and kaempferol showed strong inhibitory effects on aromatase activity and mRNA expression. We examined the anti-tumor effects of GBE on aromatase expression using a xenograft model. Androstenedione pellet was inserted into ovariectomized BALB/c-Slc-nu mice and MCF-7 AROM cells were inoculated to establish the xenograft model. Mice were given oral administration of GBE (40 to 1,000 mg/kg) for 3 weeks after tumor size was measurable (200 – 300 mm³). 200 mg/kg, and 1,000 mg/kg of GBE strongly delayed tumor growth and suppressed tumor growth compared to vehicle treated group. After three weeks treatment, the % control changes in mean tumor volume of vehicle control group was 167.35 ± 14.42% and 200 mg/kg of GBE treated group was 89.09 ± 34.23%. This study showed that GBE can be potentially useful in the treatment of hormone dependent breast cancer through the inhibition of aromatase activity as well as tumor suppression.

Keywords: Breast cancer, Aromatase inhibitor, Ginkgo biloba extract, Kaempferol, Xenograft model