Authors: Naso, Luciana Gissella; Martinez, Valeria Romina; Lezama, Luis; Salado, Clarisa; Valcarcel, María; Ferrer, Evelina Gloria; Williams, Patricia Ana María
Publication Date: 2016.
Language: English.
Abstract:
The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)3]Na5·6H2O (VOdios), has been synthesized and characterized both in solid and solution states. The interaction of the metal ion through the sugar moiety of diosmin precluded the improvement of the antioxidant effects. However, the cell-killing effects tested in human lung A549 and breast T47D, SKBR3 and MDAMB231 cancer cell lines, were enhanced by complexation. The anti-proliferative effects on the human lung cancer cell line were accompanied by cellular ROS generation and an increase in cytoplasm condensation. The breast cancer cell lines did not produce caspase3/7 activation, mitochondrial potential reduction and ROS generation. Therefore, a non-apoptotic form of cell death in a caspase- and oxidative stress-independent manner has been proposed. The protein binding ability has been monitored by the quenching of tryptophan emission in the presence of the compounds using bovine serum albumin (BSA) as a model protein. Both compounds could be distributed and transported in vivo and the complex displayed stronger binding affinity and higher contributions to the hydrogen bond and van der Waals forces.
Author affiliation: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Author affiliation: Martinez, Valeria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Author affiliation: Lezama, Luis. Universidad del País Vasco; España. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Salado, Clarisa. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Valcarcel, María. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Author affiliation: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Naso, Luciana Gissella; Lezama, Luis; Valcarcel, María; Salado, Clarisa; Villacé, Patricia; Kortazar, Danel; Ferrer, Evelina Gloria; Williams, Patricia Ana María
Publication Date: 2016.
Language: English.
Abstract:
Chemotherapy using metal coordination compounds for cancer treatment is the work of the ongoing research.Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation,a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cationhas been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na·3H2O (VOlut) were determined. The metal coordinated to two cis-deprotonated oxygen atoms (ArO−) of the ligand and two H2O molecules. Magnetic measurements in solid state indicatedthe presence of an effective exchange pathway between adjacent vanadiumions. VOlut improved the antioxidant capacity of luteolin only against hydroxyl radical. The antitumoral effects were evaluated on MDAMB231 breastcancer and A549 lung cancer cell lines. VOlut exhibited higher viability inhibition (IC50=17 μM) than the ligand on MDAMB231 cells but they have the same behavior on A549 cells (ca. IC50=60 μM). At least oxidative stressprocesses were active during cancer cell-killing. When metals chelated through the carbonyl group and one adjacent OH group of the flavonoid an effective improvement of the biological properties has been observed. In VOlut the different coordination may be the cause of the small improvement of some of the tested properties of the flavonoid. Luteolin and VOlut could be distributed and transported in vivo. Luteolin interacted in the microenvironment of the tryptophan group of the serum binding protein, BSA, by means of electrostatic forces and its complex bind the protein by H bonding and van derWaals interactions.
Author affiliation: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Author affiliation: Lezama, Luis. Universidad del País Vasco; España. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Valcarcel, María. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Salado, Clarisa. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Villacé, Patricia. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Kortazar, Danel. Parque científico y Tecnológico de Bizkaia; España
Author affiliation: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Author affiliation: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas