Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI 48201, USA.
ISTRA, Department of Microbiology, Abeda Inamdar Senior College, University of Pune Pune 411001, India.
Am J Transl Res. 2015 Feb 15;7(2):298-308. eCollection 2015.
We recently described the synthesis and characterization of a novel difluorinatedbenzylidene analog of curcumin, commonly referred as CDF, which demonstrated significantly enhanced bioavailability and in vivo anticancer activity. CDF targets many factors similar to curcumin, albeit with more potency, as reported previously. To further highlight this differential behavior of CDF, we chose matrix metalloproteinase protein MMP-2 which is involved in the processes of invasion and metastasis of human tumors. Both curcumin and CDF were characterized for their binding characteristics using in silico docking studies; they were also evaluated via biological assays involving gelatin zymography, miRNA analysis, invasion assays and ELISA. CDF was found to inhibit MMP-2 expression and activity in A549 and H1299 NSCLC cells much more effectively than curcumin, validating molecular modeling results. miR-874, an MMP-2-targeting miRNA, was up-regulated by CDF. Thus, it appears that CDF can inhibit MMP-2 through multiple mechanisms. Our results are suggestive of a more potent inhibition of invasion and metastasis by CDF, compared to curcumin, thus warranting its further evaluation as an effective anticancer agent.
我们最近描述了一种新型二氟苯并亚甲基姜黄素类似物（通常称为 CDF）的合成和表征，该类似物表现出明显增强的生物利用度和体内抗癌活性。正如之前报道的那样，CDF 针对许多与姜黄素相似的因素，但具有更高的效力。为了进一步强调 CDF 的这种差异行为，我们选择了基质金属蛋白酶蛋白 MMP-2，它参与人类肿瘤的侵袭和转移过程。我们使用计算机对接研究来表征姜黄素和 CDF 的结合特性；我们还通过涉及明胶酶谱分析、miRNA 分析、侵袭测定和 ELISA 的生物测定来评估它们。与姜黄素相比，CDF 更有效地抑制 A549 和 H1299 NSCLC 细胞中的 MMP-2 表达和活性，验证了分子建模结果。miR-874 是 MMP-2 的靶向 miRNA，被 CDF 上调。因此，CDF 似乎可以通过多种机制抑制 MMP-2。与姜黄素相比，我们的结果表明 CDF 可以更有效地抑制侵袭和转移，因此值得进一步评估其作为有效的抗癌药物。
