Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model

Verfasser / Beitragende:
[I. León, J. Cadavid-Vargas, I. Tiscornia, V. Porro, S. Castelli, P. Katkar, A. Desideri, M. Bollati-Fogolin, S. Etcheverry]
Ort, Verlag, Jahr:
2015
Enthalten in:
JBIC Journal of Biological Inorganic Chemistry, 20/7(2015-10-01), 1175-1191
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00775-015-1298-7  |2 doi 
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245 0 0 |a Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model  |h [Elektronische Daten]  |c [I. León, J. Cadavid-Vargas, I. Tiscornia, V. Porro, S. Castelli, P. Katkar, A. Desideri, M. Bollati-Fogolin, S. Etcheverry] 
520 3 |a Vanadiumcompounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na2[VO(silibinin)2]·6H2O (VOsil) and chrysin [VO(chrysin)2EtOH]2 (VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments. Graphical Abstract: 
540 |a SBIC, 2015 
690 7 |a Metal based drug  |2 nationallicence 
690 7 |a HT-29 human colon adenocarcinoma cells  |2 nationallicence 
690 7 |a Mechanisms of action  |2 nationallicence 
690 7 |a Flavonoids  |2 nationallicence 
690 7 |a Vanadium  |2 nationallicence 
700 1 |a León  |D I.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
700 1 |a Cadavid-Vargas  |D J.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
700 1 |a Tiscornia  |D I.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
700 1 |a Porro  |D V.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
700 1 |a Castelli  |D S.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
700 1 |a Katkar  |D P.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
700 1 |a Desideri  |D A.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
700 1 |a Bollati-Fogolin  |D M.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
700 1 |a Etcheverry  |D S.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
773 0 |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/7(2015-10-01), 1175-1191  |x 0949-8257  |q 20:7<1175  |1 2015  |2 20  |o 775 
856 4 0 |u https://doi.org/10.1007/s00775-015-1298-7  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00775-015-1298-7  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a León  |D I.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Cadavid-Vargas  |D J.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tiscornia  |D I.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Porro  |D V.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Castelli  |D S.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Katkar  |D P.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Desideri  |D A.  |u Department of Biology, University of Rome "Tor Vergata”, Rome, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bollati-Fogolin  |D M.  |u Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Etcheverry  |D S.  |u Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/7(2015-10-01), 1175-1191  |x 0949-8257  |q 20:7<1175  |1 2015  |2 20  |o 775