The role of ABCG2 in health and disease: Linking cancer therapy resistance and other disorders.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2024-11-17 DOI:10.1016/j.lfs.2024.123245

Nahla E El-Ashmawy, Ghada M Al-Ashmawy, Omnia B Hamada, Naglaa F Khedr

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Abstract

All biological systems have adenosine triphosphate (ATP) binding cassette (ABC) transporters, one of the significant protein superfamilies involved in transport across membranes. ABC transporters have been implicated in the etiology of diseases like metabolic disorders, cancer, and Alzheimer's disease. ATP-binding cassette superfamily G member 2 (ABCG2), one of the ABC transporters, is necessary for the ATP-dependent efflux of several endogenous and exogenous substances. Consequently, it maintained cellular homeostasis and shielded tissue from xenobiotic substances. ABCG2 was initially identified in an Adriamycin-selected breast cancer cell line (MCF-7/AdrVp) and was linked to the emergence of multidrug resistance (MDR) in cancerous cells. Under many pathophysiological conditions, including inflammation, disease pathology, tissue injury, infection, and in response to xenobiotics and endogenous substances, the expression of ABCG2 undergoes alterations that result in modifications in its function and activity. Genetic variants in the ABCG2 transporter can potentially impact its expression and function, contributing to the development of many disorders. This review aimed to illustrate the impact of ABCG2 expression and its variants on oral drug bioavailability, MDR in specific cancer cells, explore the relationship between ABCG2 expression and other disorders such as gout, Alzheimer's disease, epilepsy, and erythropoietic protoporphyria, and demonstrate the influence of various synthetic and natural compounds in regulating ABCG2 expression.

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ABCG2 在健康和疾病中的作用：癌症抗药性与其他疾病之间的联系

所有生物系统都有三磷酸腺苷（ATP）结合盒（ABC）转运体，它是参与跨膜转运的重要蛋白质超家族之一。ABC 转运体与代谢紊乱、癌症和阿尔茨海默病等疾病的病因有关。ATP结合盒超家族G成员2（ABCG2）是ABC转运体之一，是多种内源性和外源性物质的ATP依赖性外流所必需的。因此，它能维持细胞平衡，保护组织免受异生物物质的侵害。ABCG2 最初是在阿霉素筛选的乳腺癌细胞系（MCF-7/AdrVp）中发现的，并与癌细胞出现的多药耐药性（MDR）有关。在许多病理生理条件下，包括炎症、疾病病理、组织损伤、感染以及对异种生物素和内源性物质的反应，ABCG2 的表达会发生改变，从而导致其功能和活性的改变。ABCG2 转运体的基因变异可能会影响其表达和功能，从而导致许多疾病的发生。本综述旨在说明 ABCG2 的表达及其变异对口服药物生物利用度、特定癌细胞的 MDR 的影响，探讨 ABCG2 的表达与痛风、阿尔茨海默病、癫痫和红细胞生成性原卟啉症等其他疾病之间的关系，并展示各种合成化合物和天然化合物在调节 ABCG2 表达方面的影响。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.