Absence of herb-drug interactions of mistletoe with the tamoxifen metabolite (E/Z)-endoxifen and cytochrome P450 3A4/5 and 2D6 in vitro
Absence of herb-drug interactions of mistletoe with the tamoxifen metabolite (E/Z)-endoxifen and cytochrome P450 3A4/5 and 2D6 in vitro
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DOI：
10.1186/s12906-019-2439-2
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发表时间：
2019-01-18
影响因子：
--
通讯作者：
Baumgartner, S.
中科院分区：
文献类型：
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作者：
Weissenstein, U.;Kunz, M.;Baumgartner, S.
背景诊断为乳腺癌的妇女经常寻求补充和替代（CAM）治疗方案，以帮助科普其疾病和传统癌症治疗的副作用。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。治疗雌激素受体阳性乳腺癌的最古老和最常用的常规药物之一是他莫昔芬。除了他莫昔芬和槲寄生组合的积极临床经验外，对这两种产品之间可能的草药-药物相互作用（HDI）知之甚少。在目前的体外研究中，我们调查了标准化的商业槲寄生制剂的活性内昔芬，tamoxifen.MethodsThe雌激素受体阳性的人乳腺癌细胞系MCF-7的主要活性代谢产物的影响与（E/Z）-盐酸内昔芬在存在和不存在一个定义的雌二醇浓度。将每种浓度的药物与发酵的槲寄生组合。以临床相关剂量的VAE提取物（VAE），并分析增殖、凋亡和细胞周期。在平行，可能的抑制CYP 3A 4/5和CYP 2D 6进行了研究，使用50供体混合性别汇集人肝微粒体（HLM）。ResultsVAE不抑制内昔芬诱导的细胞抑制和细胞毒性。在较高浓度下，VAE显示出累加抑制作用。VAE制剂并没有引起抑制CYP 3A 4/5和CYP 2D 6催化tamoxifen metabolis.ConclusionsThe在体外结果表明，槲寄生制剂可用于与他莫昔芬没有HDIs的风险。
BackgroundWomen 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.MethodsThe 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).ResultsVAE 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.ConclusionsThe in vitro results suggest that mistletoe preparations can be used in combination with tamoxifen without the risk of HDIs.