1α,25-dihydroxyvitamin D3 inhibits C4-2 prostate cancer cell growth via a retinoblastoma protein (Rb)-independent G1 arrest.

The Prostate
Michele N WashingtonNancy L Weigel

Abstract

The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25D) reduces the growth of several prostate cancer cell lines, most commonly by inducing a cell-cycle arrest in G(1). This is mediated, in part, through down-regulation of c-Myc, a positive regulator of the transcription factor, E2F. There is evidence that prostate cancer cells lacking functional retinoblastoma protein (Rb), a negative regulator of E2F activity, are poorly responsive to 1,25D treatment. Since up to 60% of prostate cancers demonstrate a loss of heterozygosity for Rb, we sought to determine whether Rb is required for the growth inhibitory effects of 1,25D. Using siRNA, Rb was reduced in C4-2 prostate cancer cells, and the response of cells to 1,25D treatment or depletion of c-myc measured by [(3)H]-thymidine incorporation and flow cytometry. The effects of 1,25D treatment on E2F levels and activity, and E2F target gene expression were also measured. 1,25D treatment and c-Myc depletion both cause a G(1) arrest inhibiting C4-2 cell proliferation independently of Rb. 1,25D reduces c-Myc expression and causes a decrease in E2F and E2F target genes. Bcl-2, an E2F target and positive regulator of C4-2 cell growth, also is down-regulated by 1,25D indepen...Continue Reading

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Citations

Oct 3, 2013·Nutrients·Meis Moukayed, William B Grant
Aug 4, 2015·Chinese Journal of Natural Medicines·Rachel A NessWei Li
Apr 29, 2011·Cancer Biology & Therapy·Tunde O Akinyeke, LaMonica V Stewart
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Dec 10, 2020·International Journal of Molecular Sciences·Sachin Bhoora, Rivak Punchoo
Aug 8, 2021·International Journal of Molecular Sciences·Waqas AlamCarla Renata Arciola

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