title: Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages.
abstract: Three new large hexanuclear metalla-prisms 9-11 incorporating 1,3, 5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by (1)H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 μM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages.
authors.affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dubey
authors.affiliation: Department of Life Science, Gachon University, Seongnam, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Park
authors.affiliation: Department of Life Science, Gachon University, Seongnam, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kwon
authors.affiliation: Department of Life Science, Gachon University, Seongnam, Republic of Korea.
authors.forename: Yong Joon
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Taegeun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea.
authors.forename: Inhye
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Life Science, Gachon University, Seongnam, Republic of Korea.
authors.forename: Se Chan
authors.initials: SC
authors.lastname: Kang
authors.affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Ki-Whan
authors.initials: KW
authors.lastname: Chi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004610:Ellagic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D004610:Ellagic Acid; D012428:Ruthenium
keywords: G-CSF; Rantes; antioxidant; metalla-prism; tumoricidal assay