Momtazi Amir Abbas, Sahebkar Amirhossein
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Pharm Des. 2016;22(28):4386-97. doi: 10.2174/1381612822666160527113501.
Curcumin, a polyphenol from turmeric, is a dietary phytochemical with a diversity of health benefits including strong anti-tumor effects. Curcumin undergoes a rapid metabolism resulting in a low oral bioavailability. 3, 4-difluorobenzylidene curcumin or (CDF) is a novel fluorinated curcumin analogue which has been shown to be about 3 times more bioavailable than curcumin. This review aimed to summarize the findings of studies related to pharmacokinetic and pharmacological characteristics of CDF.
A systematic literature search was prformed in Scopus and Medline to identify all published articles dealing with CDF.
Biodistribution assays have revealed that curcumin is mostly distributed to the heart and lung tissues while CDF is preferentially accumulated in pancreas where its tissue concentrations reach two folds higher than that of curcumin. Moreover, CDF has been reported to possess stronger cytotoxic effects compared with CMN in both monolayer and spheroid cultures of different tumor cell lines including chemo-resistant ones. CDF can promote tumor suppression through multiple mechanisms including inhibition of self-renewal capacity of cancer stem/stem-like cells, clonogenicity invasiveness and angiogenesis of tumor cells, while increasing the sensitivity of cells to chemotherapy. These effects are the results of the modulatory action of CDF on diverse targets, such as miRNAs (miR-21, miR-101, miR-210, miR34a and miR34c), PTEN, CD44, EGFR, EpCAM, EZH2, HIF-1α, and VEGF.
This review presents an overview of the findings on metabolism and pharmacological activities of CDF, and also highlights potential opportunities to use this novel curcumin analogue in the treatment of cancer.
姜黄素是一种来自姜黄的多酚，是一种具有多种健康益处（包括强大抗肿瘤作用）的膳食植物化学物质。姜黄素代谢迅速，导致口服生物利用度较低。3,4-二氟亚苄基姜黄素（CDF）是一种新型氟化姜黄素类似物，其生物利用度比姜黄素高约3倍。本综述旨在总结与CDF的药代动力学和药理学特性相关的研究结果。
在Scopus和Medline中进行系统的文献检索，以识别所有已发表的关于CDF的文章。
生物分布分析表明，姜黄素主要分布于心和肺组织，而CDF优先在胰腺中积累，其组织浓度比姜黄素高两倍。此外，据报道，在包括化疗耐药细胞系在内的不同肿瘤细胞系的单层和球体培养中，CDF比姜黄素具有更强的细胞毒性作用。CDF可通过多种机制促进肿瘤抑制，包括抑制癌症干细胞/干细胞样细胞的自我更新能力、肿瘤细胞的克隆形成侵袭和血管生成，同时增加细胞对化疗的敏感性。这些作用是CDF对多种靶点（如miRNA（miR-21、miR-101、miR-210、miR34a和miR34c）、PTEN、CD44、EGFR、EpCAM、EZH2、HIF-1α和VEGF）调节作用的结果。
本综述概述了CDF的代谢和药理活性研究结果，并强调了使用这种新型姜黄素类似物治疗癌症的潜在机会。
