Quercetin derivatives as potent inducers of selective cytotoxicity in glioma cells.
Quercetin (Q) is a flavonoid widely distributed in the plant kingdom and well-known for its ability to exert antioxidant, prooxidant and anticarcinogenic activities in several tumor cells. Furthermore, quercetin plays an important role both in the regulation of key elements in cellular signal transduction pathways related to apoptotic cell death, and in cell cycle progression. Several studies have reported of toxic effects of Q against glioma cell lines. In this study, the effects of Q and of some Q-derivatives (acyl esters and bromo-derivatives) on U373-MG and 9L glioma cell lines survival are analyzed. The 24-hour treatment of glioma cells with several concentrations of Q (25, 50 and 100μM) did not cause any cytotoxic effects, while the administration of Q-derivatives, such as acylated and brominated quercetin, caused a sharp increase in cell death. Among all tested derivatives, 3-O-decanoylquercetin 10 manifested the strongest cytotoxic effect at a concentration as low as 25μM both in U373-MG (ca. 40% viability after 24h) and in 9L cells (ca. 20% viability after 24h). The cytotoxic effects of the Q-derivatives 3 and 10-13 were proven to be satisfactorily selective for glioma cells. When Q-derivatives were in fact administered to mouse primary astroglial or human fibroblast cell cultures, a higher cell survival rate (~90-70% and 55-45%, respectively) was observed relative to that detected in glioma cells. These results prove that selective esterification and bromination of Q increase to a great extent the toxicity of this polyphenol against glioma cells, thereby providing a possible new tool for cyto-specific glioma therapy.
Institute of Neurological Sciences of Italian National Research Council, via P. Gaifami 18, I-95126, Catania, Italy. Electronic address: paola.dellalbani@cnr.it.
Paola
P
Dell'Albani
Institute of Neurological Sciences of Italian National Research Council, via P. Gaifami 18, I-95126, Catania, Italy.
Barbara
B
Di Marco
Institute of Neurological Sciences of Italian National Research Council, via P. Gaifami 18, I-95126, Catania, Italy.
Sonia
S
Grasso
Institute of Biomolecular Chemistry of Italian National Research Council, via P. Gaifami 18, I-95126, Catania, Italy.
Concetta
C
Rocco
Institute of Biomolecular Chemistry of Italian National Research Council, via P. Gaifami 18, I-95126, Catania, Italy. Electronic address: mario.foti@cnr.it.
Mario C
MC
Foti
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D015996:Survival Rate
D000975:Antioxidants; D011794:Quercetin
3-O-decanoylquercetin (PubChem CID: 0); 6,8-Dibromo-3-O-palmitoylquercetin (PubChem CID: 0); Apoptosis; Caspase-3; Glioma cells; Quercetin; Quercetin pentaacetate (PubChem CID: 14005); Selective cytotoxicity; Signal transduction