title: Butein induces apoptosis and inhibits prostate tumor growth in vitro and in vivo.
abstract: OBJECTIVE
  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) and Thr(308), (iii) nuclear factor-kappa B (NF-κB) and IκB kinaseα, (iv) degradation and phosphorylation of IκBα, (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.
  
  
  METHODS
  For the first time, we have shown that butein caused inhibition of prostate tumor growth in-vivo.
  
  
  CONCLUSIONS
  We suggest that butein could be developed as an agent against PCa. Antioxid. Redox Signal. 16, 1195-1204.
authors: Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
authors: Naghma
authors: N
authors: Khan
authors: Vaqar M
authors: VM
authors: Adhami
authors: Farrukh
authors: F
authors: Afaq
authors: Hasan
authors: H
authors: Mukhtar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D059748:Proteolysis
chemical_list: D018797:Cell Cycle Proteins; D047188:Chalcones; C040918:butein; D020169:Caspases