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Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages.

Dubey A, Park DW, Kwon JE, Jeong YJ, Kim T, Kim I, Kang SC, Chi KW - Int J Nanomedicine (2015)

Bottom Line: Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic representing the proposed events and G-CSF and Rantes gene expression in RAW264.7 macrophages with ellagic acid (control) and compound 10.Notes: The upward arrows indicate an increase in the G-CSF level and the crossed arrow indicates the inhibition of Rantes.Abbreviations: Rantes, regulated on activation normal T cell expressed and secreted; G-CSF, granulocyte-colony stimulating factor.
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f7-ijn-10-227: Schematic representing the proposed events and G-CSF and Rantes gene expression in RAW264.7 macrophages with ellagic acid (control) and compound 10.Notes: The upward arrows indicate an increase in the G-CSF level and the crossed arrow indicates the inhibition of Rantes.Abbreviations: Rantes, regulated on activation normal T cell expressed and secreted; G-CSF, granulocyte-colony stimulating factor.

Mentions: The inhibition of tumor cell growth exerted by compound 10 was apparently through the modulation of a different set of macrophage proteins than those affected by the naked ellagic acid. While ellagic acid encapsulated in compound 10 acted on G-CSF and Rantes, the naked ellagic acid had an effect on IFN-γ secretion or protein expression (Figure 6). In order to confirm these results, we investigated the mRNA expression of G-CSF and Rantes in the macrophage RAW264.7 cell line by using the real-time polymerase chain reaction. G-CSF was increased by compound 10 (~2.1 times vs control) and Rantes was decreased (~0.4 times vs control) with respect to the mRNA levels (Figure 7). These results demonstrate that ellagic acid encapsulated into a nano-sized metalla-cage inhibited tumor cells through the modulation of G-CSF and Rantes in macrophages at the level of both protein and mRNA.


Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages.

Dubey A, Park DW, Kwon JE, Jeong YJ, Kim T, Kim I, Kang SC, Chi KW - Int J Nanomedicine (2015)

Schematic representing the proposed events and G-CSF and Rantes gene expression in RAW264.7 macrophages with ellagic acid (control) and compound 10.Notes: The upward arrows indicate an increase in the G-CSF level and the crossed arrow indicates the inhibition of Rantes.Abbreviations: Rantes, regulated on activation normal T cell expressed and secreted; G-CSF, granulocyte-colony stimulating factor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562765&req=5

f7-ijn-10-227: Schematic representing the proposed events and G-CSF and Rantes gene expression in RAW264.7 macrophages with ellagic acid (control) and compound 10.Notes: The upward arrows indicate an increase in the G-CSF level and the crossed arrow indicates the inhibition of Rantes.Abbreviations: Rantes, regulated on activation normal T cell expressed and secreted; G-CSF, granulocyte-colony stimulating factor.
Mentions: The inhibition of tumor cell growth exerted by compound 10 was apparently through the modulation of a different set of macrophage proteins than those affected by the naked ellagic acid. While ellagic acid encapsulated in compound 10 acted on G-CSF and Rantes, the naked ellagic acid had an effect on IFN-γ secretion or protein expression (Figure 6). In order to confirm these results, we investigated the mRNA expression of G-CSF and Rantes in the macrophage RAW264.7 cell line by using the real-time polymerase chain reaction. G-CSF was increased by compound 10 (~2.1 times vs control) and Rantes was decreased (~0.4 times vs control) with respect to the mRNA levels (Figure 7). These results demonstrate that ellagic acid encapsulated into a nano-sized metalla-cage inhibited tumor cells through the modulation of G-CSF and Rantes in macrophages at the level of both protein and mRNA.

Bottom Line: Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus