Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1 Degradation.
Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1 Degradation.
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芸香碱通过 MARCH8 依赖性 ABCB1 降解提高耐药细胞的抗癌药物敏感性
DOI：
10.3390/biomedicines9091143
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发表时间：
2021-09-02
期刊：
影响因子：
4.7
通讯作者：
Lin Z
中科院分区：
文献类型：
--
作者：
Zou T;Zeng C;Qu J;Yan X;Lin Z
The overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) subfamily B member 1 (ABCB1; P-glycoprotein; MDR1) in some types of cancer cells is one of the mechanisms responsible for the development of multidrug resistance (MDR), which leads to the failure of chemotherapy. Therefore, it is important to inhibit the activity or reduce the expression level of ABCB1 to maintain an effective intracellular level of chemotherapeutic drugs. In this study, we found that rutaecarpine, a bioactive alkaloid isolated from Evodia Rutaecarpa, has the capacity to reverse ABCB1-mediated MDR. Our data indicated that the reversal effect of rutaecarpine was related to the attenuation of the protein level of ABCB1. Mechanistically, we demonstrated that ABCB1 is a newly discovered substrate of E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8). MARCH8 can interact with ABCB1 and promote its ubiquitination and degradation. In short, rutaecarpine increased the degradation of ABCB1 protein by upregulating the protein level of MARCH8, thereby antagonizing ABCB1-mediated MDR. Notably, the treatment of rutaecarpine combined with other anticancer drugs exhibits a therapeutic effect on transplanted tumors. Therefore, our study provides a potential chemotherapeutic strategy of co-administrating rutaecarpine with other conventional chemotherapeutic agents to overcome MDR and improve therapeutic effect.
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DOI：
10.3390/molecules15031873
发表时间：
2010-03-15
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Jia S;Hu C
通讯作者：
Hu C
影响因子：
--
作者：
Fan J;Tian L;Li M;Huang SH;Zhang J;Zhao B
通讯作者：
Zhao B
影响因子：
20.3
作者：
Damiano, JS;Cress, AE;Dalton, WS
通讯作者：
Dalton, WS
影响因子：
5.4
作者：
Bartee, E;Mansouri, M;Früh, K
通讯作者：
Früh, K
影响因子：
4.3
作者：
Landreville S;Agapova OA;Kneass ZT;Salesse C;Harbour JW
通讯作者：
Harbour JW