Society for Cancer Research, Hiscia Institute, Arlesheim, Switzerland.
Iscador AG, Arlesheim, Switzerland.
BMC Complement Altern Med. 2019 Jan 18;19(1):23. doi: 10.1186/s12906-019-2439-2.
Women diagnosed with breast cancer frequently seek complementary and alternative (CAM) treatment options that can help to cope with their disease and the side effects of conventional cancer therapy. Especially in Europe, breast cancer patients use herbal products containing mistletoe (Viscum album L.). The oldest and one of the most prescribed conventional drugs for the treatment of estrogen receptor positive breast cancer is tamoxifen. Aside from positive clinical experience with the combination of tamoxifen and mistletoe, little is known about possible herb-drug interactions (HDIs) between the two products. In the present in vitro study, we investigated the effect of standardized commercial mistletoe preparations on the activity of endoxifen, the major active metabolite of tamoxifen.
The estrogen receptor positive human breast carcinoma cell line MCF-7 was treated with (E/Z)-endoxifen hydrochloride in the presence and absence of a defined estradiol concentration. Each concentration of the drug was combined with fermented Viscum album L. extracts (VAE) at clinically relevant doses, and proliferation, apoptosis and cell cycle were analyzed. In parallel, possible inhibition of CYP3A4/5 and CYP2D6 was investigated using 50-donor mixed gender pooled human liver microsomes (HLMs).
VAE did not inhibit endoxifen induced cytostasis and cytotoxicity. At higher concentrations, VAE showed an additive inhibitory effect. VAE preparations did not cause inhibition of CYP3A4/5 and CYP2D6 catalyzed tamoxifen metabolism.
The in vitro results suggest that mistletoe preparations can be used in combination with tamoxifen without the risk of HDIs.
被诊断患有乳腺癌的女性经常会寻求补充和替代（CAM）治疗方案，以帮助应对疾病和常规癌症治疗的副作用。特别是在欧洲，乳腺癌患者使用含有槲寄生（Viscum album L.）的草药产品。他莫昔芬是治疗雌激素受体阳性乳腺癌最古老和最常用的常规药物之一。除了与槲寄生联合使用的积极临床经验外，对于这两种产品之间可能存在的草药-药物相互作用（HDIs）知之甚少。在本体外研究中，我们研究了标准化商业槲寄生制剂对他莫昔芬主要活性代谢物(endoxifen)活性的影响。
用（E/Z）-endoxifen 盐酸盐处理雌激素受体阳性人乳腺癌细胞系 MCF-7，存在和不存在定义的雌二醇浓度。每种药物浓度均与临床相关剂量的发酵槲寄生提取物（VAE）组合，并分析增殖、凋亡和细胞周期。同时，使用 50 名供体混合性别人肝微粒体（HLM）研究了 CYP3A4/5 和 CYP2D6 抑制的可能性。
VAE 不会抑制 endoxifen 诱导的细胞停滞和细胞毒性。在较高浓度下，VAE 表现出相加抑制作用。VAE 制剂不会引起 CYP3A4/5 和 CYP2D6 催化的他莫昔芬代谢抑制。
体外结果表明，槲寄生制剂可以与他莫昔芬联合使用，而不会有 HDIs 的风险。
