Butein induces apoptosis and inhibits prostate tumor growth in Vitro and in Vivo

Academic Article

Abstract

  • Aim: Prostate cancer (PCa) is one of the most common cancers in men in the United States with similar trends 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 μM; 48 h) caused a decrease in viability of PCa cells but had only a minimal effect on normal prostate epithelial cells. In butein-treated cells, there was a 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) phosphatidylinositol 3-kinase (p85 and p110), (ii) phosphorylation of Akt at both Ser 473 Thr 308, (iii) nuclear factor-kappa B (NF-κB) and IκB kinasea,α (iv) degradation and phosphorylation of IκB,(v) NF-κB DNA-binding activity, (vi) induction of apoptosis, and (vii) Poly (ADP-ribose) polymerase 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 a significant inhibition of tumor growth with a decrease in the serum prostate-specific antigen 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. © 2012 Mary Ann Liebert, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Khan N; Adhami VM; Afaq F; Mukhtar H
  • Start Page

  • 1195
  • End Page

  • 1204
  • Volume

  • 16
  • Issue

  • 11