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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

Tumoricidal effects of ellagic acid (5) and compound 10 on co-cultured B16/F10 mouse skin carcinoma and RAW264.7 mouse macrophage cells. (A) Ellagic acid (5) and compound 10 without macrophage pretreatment. (B) Elicited macrophages pretreated with ellagic acid (5) and compound 10 24 hours before incubation with B16 cells.Notes: The results are mean ± SE of triplicates from a representative experiment. **P<0.01; significantly different from the control.Abbreviation: SE, standard error.
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f5-ijn-10-227: Tumoricidal effects of ellagic acid (5) and compound 10 on co-cultured B16/F10 mouse skin carcinoma and RAW264.7 mouse macrophage cells. (A) Ellagic acid (5) and compound 10 without macrophage pretreatment. (B) Elicited macrophages pretreated with ellagic acid (5) and compound 10 24 hours before incubation with B16 cells.Notes: The results are mean ± SE of triplicates from a representative experiment. **P<0.01; significantly different from the control.Abbreviation: SE, standard error.

Mentions: Cells of the monocyte–macrophage lineage have the capacity to recognize and destroy tumor cells50,51 when activated by lymphokines such as IFN-γ and G-CSF.52,53 In this study, macrophages were pretreated with the test materials (ellagic acid [5] and cage 10) or the control medium, before being co-cultured with B16/F10 cells to assess the ability of the compounds to activate macrophages to kill tumor cells. Figure 5A indicated that ellagic acid and compound 10 did not exert cytotoxic effects but doxorubicin did in B16/F10 mouse skin carcinoma when these were incubated without macrophages. Figure 5B showed that ellagic acid and compound 10 incubated with macrophages kill 55.1% (at 2 μM of ellagic acid) and 58.6% (at 2 μM of compound 10) of cancer cells compared to the untreated macrophages with B16/F10 cells whereas doxorubicin was less effective compared to its effect without macrophages. Therefore, ellagic acid and compound 10 are macrophage-dependent in terms of their cytotoxicity against cancer cells.


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)

Tumoricidal effects of ellagic acid (5) and compound 10 on co-cultured B16/F10 mouse skin carcinoma and RAW264.7 mouse macrophage cells. (A) Ellagic acid (5) and compound 10 without macrophage pretreatment. (B) Elicited macrophages pretreated with ellagic acid (5) and compound 10 24 hours before incubation with B16 cells.Notes: The results are mean ± SE of triplicates from a representative experiment. **P<0.01; significantly different from the control.Abbreviation: SE, standard error.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-10-227: Tumoricidal effects of ellagic acid (5) and compound 10 on co-cultured B16/F10 mouse skin carcinoma and RAW264.7 mouse macrophage cells. (A) Ellagic acid (5) and compound 10 without macrophage pretreatment. (B) Elicited macrophages pretreated with ellagic acid (5) and compound 10 24 hours before incubation with B16 cells.Notes: The results are mean ± SE of triplicates from a representative experiment. **P<0.01; significantly different from the control.Abbreviation: SE, standard error.
Mentions: Cells of the monocyte–macrophage lineage have the capacity to recognize and destroy tumor cells50,51 when activated by lymphokines such as IFN-γ and G-CSF.52,53 In this study, macrophages were pretreated with the test materials (ellagic acid [5] and cage 10) or the control medium, before being co-cultured with B16/F10 cells to assess the ability of the compounds to activate macrophages to kill tumor cells. Figure 5A indicated that ellagic acid and compound 10 did not exert cytotoxic effects but doxorubicin did in B16/F10 mouse skin carcinoma when these were incubated without macrophages. Figure 5B showed that ellagic acid and compound 10 incubated with macrophages kill 55.1% (at 2 μM of ellagic acid) and 58.6% (at 2 μM of compound 10) of cancer cells compared to the untreated macrophages with B16/F10 cells whereas doxorubicin was less effective compared to its effect without macrophages. Therefore, ellagic acid and compound 10 are macrophage-dependent in terms of their cytotoxicity against cancer cells.

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