title: Molecular docking and inhibition of matrix metalloproteinase-2 by novel difluorinatedbenzylidene curcumin analog.
abstract: 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.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI 48201, USA.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: ISTRA, Department of Microbiology, Abeda Inamdar Senior College, University of Pune Pune 411001, India.
authors.forename: Afreen
authors.initials: A
authors.lastname: Sayed
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI 48201, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Ginnebaugh
authors.affiliation: Tata Consultancy Services Hinjewadi, Pune, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Tata Consultancy Services Hinjewadi, Pune, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Suri
authors.affiliation: Tata Consultancy Services Hinjewadi, Pune, India.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Saraph
authors.affiliation: ISTRA, Department of Chemistry, Abeda Inamdar Senior College, University of Pune Pune 411001, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI 48201, USA ; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI 48201, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
keywords: CDF; MMP-2; curcumin; in silico molecular docking; miR-874