Akbariani Mostafa, Omidi Mahmoud, Shahabi Zohreh, Haghi-Aminjan Hamed, Shadboorestan Amir
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Food Health Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Cancer Cell Int. 2025 Jan 28;25(1):27. doi: 10.1186/s12935-024-03622-9.
Cancer remains a leading cause of death worldwide. Environmental factors, specifically endocrine-disrupting chemicals (EDCs), like phthalates, are increasingly being linked to cancer development. Phthalates, widely used in consumer products, can activate the aryl hydrocarbon receptor (AhR). This scoping review investigates how phthalate exposure influences cancer-related molecular pathways through the regulation of the AhR pathway to uncover the underlying mechanisms.
We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science (ISI) database up to November 2023. Studies were selected based on peer-reviewed status, focus on phthalates' effects on cancer through the AhR pathway and the availability of full texts. Data extraction emphasized study models, types of phthalates, exposure protocols, and cancer-related signaling pathway outcomes.
Out of 108 initial articles, 10 met the inclusion criteria. Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite Mono (2-ethylhexyl) phthalate (MEHP) were found to promote cancer cell proliferation, epithelial-mesenchymal transition (EMT), and chemoresistance through the AhR pathway. Specifically, DEHP activated AhR, leading to elevated expression of EMT markers, increased cancer stem cell populations, and enhanced drug metabolism and resistance. Other phthalates, such as Butyl Benzyl Phthalate (BBP), also activated AhR-mediated pathways, promoting angiogenesis and metastasis.
Phthalates activate the AhR pathway, contributing to cancer progression underscoring the need for developing effective interventions against phthalate-induced carcinogenesis. Regulatory measures to minimize phthalate exposure are crucial to preventing harmful health effects and improving cancer treatment outcomes.
癌症仍是全球主要的死亡原因。环境因素，特别是内分泌干扰化学物质（EDCs），如邻苯二甲酸盐，越来越多地与癌症发展相关联。广泛用于消费品中的邻苯二甲酸盐可激活芳烃受体（AhR）。本综述旨在研究邻苯二甲酸盐暴露如何通过调节AhR途径影响癌症相关分子途径，以揭示潜在机制。
我们在PubMed、Scopus和科学网（ISI）数据库中进行了全面的文献检索，截至2023年11月。根据同行评审状态、关注邻苯二甲酸盐通过AhR途径对癌症的影响以及全文可用性选择研究。数据提取重点关注研究模型、邻苯二甲酸盐类型、暴露方案以及癌症相关信号通路结果。
在108篇初始文章中，10篇符合纳入标准。发现邻苯二甲酸二（2-乙基己基）酯（DEHP）及其代谢物单（2-乙基己基）邻苯二甲酸酯（MEHP）通过AhR途径促进癌细胞增殖、上皮-间质转化（EMT）和化疗耐药性。具体而言，DEHP激活AhR，导致EMT标志物表达升高、癌症干细胞群体增加以及药物代谢和耐药性增强。其他邻苯二甲酸盐，如邻苯二甲酸丁苄酯（BBP），也激活AhR介导的途径，促进血管生成和转移。
邻苯二甲酸盐激活AhR途径，促进癌症进展，强调需要开发针对邻苯二甲酸盐诱导致癌作用的有效干预措施。尽量减少邻苯二甲酸盐暴露的监管措施对于预防有害健康影响和改善癌症治疗结果至关重要。
