Methoxychalcone induces cell-cycle arrest and apoptosis in human hormone-resistant prostate cancer cells through PI 3-kinase-independent inhibition of mTOR pathways

The Prostate
Yu-Wei SunJih-Hwa Guh

Abstract

Chalcones are contained in fruits and vegetables, and have been suggested to display anticancer activities. In this study, the anticancer mechanism of WJ9708011 (a methoxychalcone derivative) was delineated in human prostate cancer cells. Cell proliferation was examined by sulforhodamine B and clonogenic assays. Cell-cycle progression and mitochondrial membrane potential (DeltaPsi(m)) were detected by flow cytometric analysis. Expressions of protein and mRNA were detected by Western blot and RT-PCR technique, respectively. The protein synthesis was examined by [(3)H]leucine incorporation assay. The overexpression or knockdown techniques for specific target protein were also used in this study. WJ9708011 induced time- and concentration-dependent G1 arrest of the cell cycle and subsequent apoptosis in human prostate cancer cells. The G1-arrest effect was confirmed by down-regulated expressions of several G1-phase regulators, including cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)-4, Cdk2, phospho-RB, E2F-1, and Cdc25A. The mRNA expressions of cyclin D1 and cyclin E were also inhibited through the suppression of NF-kappaB. WJ9708011 blocked the protein synthesis and inhibited mammalian target of rapamycin (mTOR) signaling pat...Continue Reading

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Citations

Dec 21, 2010·BJU International·Stephan MadersbacherAndrea Tubaro
Mar 28, 2012·Chemico-biological Interactions·Che-Jen HsiaoChi-Li Chung
May 26, 2015·European Journal of Medicinal Chemistry·Debarshi Kar MahapatraVivek Asati
Mar 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong WangZhi-Hua Chen

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