Butein induces apoptosis and inhibits prostate tumor growth in-vitro and in-vivo
Menée in vitro et sur un modèle murin, cette étude montre que la butéine, une molécule de la famille des flavonoïdes, peut induire l'apoptose des cellules cancéreuses de la prostate et inhiber la croissance tumorale
Aim: Prostate cancer (PCa) is one of the most common cancers in men in the United States with similar trend worldwide. For several reasons, it is an ideal candidate disease for intervention with dietary botanical antioxidants. Indeed, many botanical antioxidants are showing promise for chemoprevention of PCa. Here, we determined the effect of an antioxidant butein (3,4,2',4'-tetrahydroxychalone) on cell-growth, apoptosis and signaling pathways in human PCa cells in-vitro and on tumor growth in athymic nude mice. Results: Treatment with butein (10-30 microM; 48 h) caused decrease in viability of PCa cells but had only minimal effect on normal prostate epithelial PrEC cells. In butein-treated cells, there was marked decrease in the protein expression of cyclins D1, D2 and E and cdks 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Treatment of cells with butein caused inhibition of (i) PI3K (p85 and p110), (ii) phosphorylation of Akt at both Ser473 and Thr308, (iii) NF-kappaB and IKKalpha, (iv) degradation and phosphorylation of IkappaBalpha, (v) NF-kappaB DNA-binding activity, (vi) induction of apoptosis, and (vii) PARP cleavage with activation of caspases-3, -8 and -9. Pretreatment of cells with caspase inhibitor (Z-VAD-FMK) blocked butein-induced activation of caspases. In athymic nude mice implanted with human PCa cells, butein caused significant inhibition of tumor growth with decrease in the serum prostate-specific antigen (PSA) levels. Innovation: For the first time, we have shown that butein caused inhibition of prostate tumor growth in-vivo. Conclusion: We suggest that butein could be developed as an agent against PCa.