Park Yong Joo, Ahn Hui Yeon, Kim Ha Ryong, Chung Kyu Hyuck, Oh Seung Min
School of Pharmacy, Sungkyunkwan University, 300, Suwon, Gyeonggi-do, 440-746, Republic of Korea.
Department of Nanofusion Technology, Hoseo University, Asan, Chungnam, 31499, Republic of Korea.
Food Chem Toxicol. 2016 Jan;87:157-65. doi: 10.1016/j.fct.2015.12.007. Epub 2015 Dec 17.
Ginkgo biloba has been used in herbal medicines for thousands of years. Although a standard G. biloba extract, EGb 761 has been used to improve cognition in breast cancer patients, its effects on breast cancer are unknown. Therefore, we investigated the antitumorigenic effects of EGb 761 using an in vitro cell model and an in vivo xenograft model. EGb 761 significantly inhibited aromatase activity in aromatase over-expressing MCF-7 cells (MCF-7 AROM). In addition, EGb 761 exposure reduced cytochrome p450 aromatase (CYP19) mRNA and protein expression; CYP19 promoter I.3 and PII expression particularly decreased. These inhibitory effects on aromatase were accompanied by reduced 17β-estradiol levels in MCF-7 AROM cells. For elucidating antitumorigenic effects, MCF-7 AROM cells were implanted in BALB/c nude mice prior to oral EGb 761 treatment for 3 weeks. EGb 761 reduced the tumor size and significantly reduced tumor CYP19 mRNA expression. Taken together, our results indicated that EGb 761 inhibited aromatase and exerted antitumor effects on breast cancer cells both in vitro and in vivo. These findings suggest that EGb761 may be a useful aromatase inhibitor for the treatment for estrogen-sensitive breast cancer.
银杏已被用于草药治疗达数千年之久。尽管一种标准化的银杏提取物EGb 761已被用于改善乳腺癌患者的认知能力,但其对乳腺癌的影响尚不清楚。因此,我们使用体外细胞模型和体内异种移植模型研究了EGb 761的抗肿瘤作用。EGb 761显著抑制了过表达芳香化酶的MCF-7细胞(MCF-7 AROM)中的芳香化酶活性。此外,EGb 761处理降低了细胞色素P450芳香化酶(CYP19)的mRNA和蛋白表达;CYP19启动子I.3和PII的表达尤其降低。这些对芳香化酶的抑制作用伴随着MCF-7 AROM细胞中17β-雌二醇水平的降低。为了阐明抗肿瘤作用,在口服EGb 761处理3周之前,将MCF-7 AROM细胞植入BALB/c裸鼠体内。EGb 761减小了肿瘤大小,并显著降低了肿瘤CYP19 mRNA表达。综上所述,我们的结果表明EGb 761抑制芳香化酶,并在体外和体内对乳腺癌细胞发挥抗肿瘤作用。这些发现表明,EGb761可能是一种用于治疗雌激素敏感性乳腺癌的有用的芳香化酶抑制剂。