title: Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model.
abstract: Vanadium compounds 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)₂2]·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.
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina.|Centro de Química Inorgánica (CEQUINOR-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina.
authors.forename: I E
authors.initials: IE
authors.lastname: León
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina.|Centro de Química Inorgánica (CEQUINOR-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina.
authors.forename: J F
authors.initials: JF
authors.lastname: Cadavid-Vargas
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
authors.forename: I
authors.initials: I
authors.lastname: Tiscornia
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
authors.forename: V
authors.initials: V
authors.lastname: Porro
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Castelli
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Katkar
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Desideri
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
authors.forename: M
authors.initials: M
authors.lastname: Bollati-Fogolin
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina. etcheverry@biol.unlp.edu.ar.|Centro de Química Inorgánica (CEQUINOR-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina. etcheverry@biol.unlp.edu.ar.
authors.forename: S B
authors.initials: SB
authors.lastname: Etcheverry
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry; D014639:Vanadium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005419:Flavonoids; D012838:Silymarin; D014639:Vanadium; C043561:chrysin; D000077385:Silybin; D002945:Cisplatin
keywords: Flavonoids; HT-29 human colon adenocarcinoma cells; Mechanisms of action; Metal based drug; Vanadium