Differential effects of quercetin and silymarin on arsenite-induced cytotoxicity in two human breast adenocarcinoma cell lines.
Arsenic has been proposed as a chemotherapeutic agent for leukemia and other solid tumors. However, its environmental exposure has been linked epidemiologically with an elevated carcinoma risk (i.e. skin, bladder and lung), with cellular oxidative stress being implicated in both induced-arsenic toxicity and carcinogenicity. Consequently, antioxidants may differentially interfere in these effects. The human mammary adenocarcinoma lines MCF-7 and ZR-75-1 were treated in vitro with 200 microM NaAsO(2) (As), 5 microM silymarin (S) and/or 50 microM quercetin (Q). The following biomembrane parameters were assessed: sialic acid (SA) in gangliosides, gamma-glutamyltranspeptidase activity (GGT), conjugated dienes and free radical activity, in order to evaluate the arsenite-flavonoid interactions. The time-dependent arsenite toxicity was not prevented by flavonoids in ZR-75-1 cells, whereas quercetin protected MCF-7 cells for 8 h. With regard to GGT, only quercetin protected ZR-75-1 cells against stress. In MCF-7 cells, the arsenite-induced GGT activity was not counteracted by either quercetin or silymarin. S, Q, As and As + S treatments reduced the SA content only in the MCF-7 membrane, while As + Q treatment increased it in both lines. The membrane resistance to lipid oxidation in these cells enclosed the up-regulation of GGT activity and sialylglycolipid content. Taking these results together, quercetin interfered with arsenite toxicity, whereas silymarin was not able. Thus, the potential role of flavonoids as co-adjutants may differ widely in therapeutic protocols.
Soria
Elio A
EA
1a Cátedra de Biología Celular, Histología y Embriología, Instituto de Biología Celular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
Eynard
Aldo R
AR
Quiroga
Patricia L
PL
Bongiovanni
Guillermina A
GA
D018053:Arsenites / Q000633:toxicity*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D018053:Arsenites; D005609:Free Radicals; D012838:Silymarin; D017670:Sodium Compounds; C017947:sodium arsenite; D011794:Quercetin; D005723:gamma-Glutamyltransferase; D019158:N-Acetylneuraminic Acid