BACKGROUND 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. METHODS A systematic literature search was prformed in Scopus and Medline to identify all published articles dealing with CDF. RESULTS 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. CONCLUSION 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.

中文翻译：

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二氟姜黄素：具有改善的抗肿瘤活性和药代动力学特征的有前途的姜黄素类似物。

背景技术姜黄素，一种来自姜黄的多酚，是一种饮食植物化学物质，具有多种健康益处，包括强大的抗肿瘤作用。姜黄素快速代谢，导致口服生物利用度低。3、4-二氟亚苄基姜黄素或（CDF）是一种新型的氟化姜黄素类似物，已显示其生物利用度比姜黄素高约3倍。这篇综述旨在总结与CDF的药代动力学和药理学特征有关的研究结果。方法在Scopus和Medline中进行系统的文献检索，以鉴定所有涉及CDF的已发表文章。结果生物分布测定表明，姜黄素主要分布于心脏和肺组织，而CDF优先积累在胰腺中，胰腺的组织浓度比姜黄素高两倍。此外，据报道，在包括化学抗性的不同肿瘤细胞系的单层和球形培养物中，与CMN相比，CDF具有更强的细胞毒性作用。CDF可以通过多种机制促进肿瘤抑制，包括抑制癌症干/干样细胞的自我更新能力，克隆性侵袭性和肿瘤细胞的血管生成，同时增加细胞对化疗的敏感性。这些效果是CDF对多种靶标（例如miRNA（miR-21，miR-101，miR-210，miR34a和miR34c），PTEN，CD44，EGFR，EpCAM，EZH2，HIF-1α和VEGF。结论本综述概述了CDF的代谢和药理活性，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。