Antipsychotic drugs inhibit the function of breast cancer resistance protein.
Antipsychotic drugs inhibit the function of breast cancer resistance protein.
复制标题
抗精神病药物会抑制乳腺癌耐药蛋白的功能。
DOI：
10.1111/j.1742-7843.2008.00298.x
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发表时间：
2008
影响因子：
3.1
通讯作者：
Devane,CLindsay
中科院分区：
文献类型：
--
作者：
Wang,Jun-Sheng;Zhu,Hao-Jie;Markowitz,JohnS;Donovan,JenniferL;Yuan,Hong-Jie;Devane,CLindsay
The ABCG2 transporter breast cancer resistance protein (BCRP) has been identified in several physiological sites. It has been suggested to play an important role in disposition of many drugs and environmental toxins. We investigated the effects of several antipsychotic drugs, including risperidone, 9‐hydroxy‐risperidone (paliperidone), olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine, and a positive control inhibitor Ko143 on functions of BCRP in MCF7 and BCRP over‐expressing MCF7/MX100 cell lines using a BCRP prototypical substrate mitoxantrone. Our findings indicated that the tested antipsychotics rank order of potency of inhibition of BCRP according to concentrations required to reach 50% of maximum inhibition (IC50) was as follows: Ko143 (0.07 µM) > risperidone (38.1 µM) > clozapine (42.0 µM) > paliperidone (51 µM) > chlorpromazine (52.2 µM) > quetiapine (66.1 µM) > olanzapine = haloperidol (>100.0 µM). We further tested the effects of various concentrations of risperidone on the BCRP‐mediated transport of oestrone‐3‐sulfate in a colon carcinoma cell line, Caco‐2, a widely used model to study drug absorption. Our findings show that risperidone at concentrations ranging from 1 to 100 µM significantly inhibited intracellular accumulation of oestrone‐3‐sulfate in Caco‐2 cell monolayers. The present results suggest that a potential source of pharmacokinetic interactions exists between BCRP substrates and several antipsychotics.
