Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells.
Glioma is the most frequent and malignant primary human brain tumor with dismal prognosis despite multimodal therapy. Resveratrol and quercetin, two structurally related and naturally occurring polyphenols, are proposed to have anticancer effects. We report here that resveratrol and quercetin decreased the cell number in four glioma cell lines but not in rat astrocytes. Low doses of resveratrol (10 microM) or quercetin (25 microM) separately had no effect on apoptosis induction, but had a strong effect on caspase 3/7 activation when administered together. Western blot analyses showed that resveratrol (10 microM) and quercetin (25 microM) caused a reduction in phosphorylation of Akt, but this reduction was not sufficient by itself to mediate the effects of these polyphenols. Most important, resveratrol and quercetin chronically administered presented a strong synergism in inducing senescence-like growth arrest. These results suggest that the combination of polyphenols can potentialize their antitumoral activity, thereby reducing the therapeutic concentration needed for glioma treatment.
Zamin
Lauren L
LL
Biophysics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Filippi-Chiela
Eduardo C
EC
Dillenburg-Pilla
Patricia
P
Horn
Fabiana
F
Salbego
Christianne
C
Lenz
Guido
G
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D004357:Drug Synergism; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004338:Drug Combinations; D013267:Stilbenes; D011794:Quercetin; D020169:Caspases; D000077185:Resveratrol