Editor's ChoiceProstate Cancer

Probing Broccoli's Benefits for Prostate Cancer

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Science Translational Medicine  07 Oct 2009:
Vol. 1, Issue 1, pp. 1ec4
DOI: 10.1126/scitranslmed.3000437

Eating cruciferous vegetables like cabbage, broccoli, and cauliflower has been linked in epidemiological studies to a reduced risk for prostate cancer, but a clear molecular explanation for this effect is lacking. One compound obtained from such vegetables—sulforaphane—inhibits prostate cancer in animal models, suggesting that it might be effective in humans as well. Sulforaphane inhibits histone deacetylases (HDACs), enzymes that remove acetyl groups from histones or nonhistone proteins, modifying their function. The substrates of one nonhistone HDAC, HDAC6, include the HSP90 chaperone protein. Upon deacetylation by HDAC6, HSP90 displays enhanced binding to the androgen receptor, which in turn becomes more stable. These observations are interesting because androgen receptor signaling is an important therapeutic target in prostate cancer. Whether sulforaphane affects HDAC6, however, is not known. Now Gibbs et al. report that in an in vitro enzyme assay, sulforaphane inhibits HDAC6. Furthermore, they show that sulforaphane treatment enhances HSP90 acetylation in human prostate cancer cell lines, leading to dissociation of HSP90 from the androgen receptor, degradation of the androgen receptor protein, and a reduction in androgen receptor–target gene expression. Thus, sulforaphane appears to deactivate HDAC6-mediated HSP90 deacetylation and thereby destabilize the androgen receptor. Although it is not yet known whether sulforaphane might be used to prevent or treat prostate cancer in humans, the pathway described by Gibbs et al. represents a possible way to interfere with androgen receptor signaling—and another reason to eat those vegetables.

A. Gibbs et al., Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc. Natl. Acad. Sci. U.S.A. 106, 16663–16668 (2009). http://www.pnas.org/content/early/2009/09/14/0908908106.full.pdf, http://www.pnas.org/content/early/2009/09/14/0908908106.html

Citation: H. B. McDonald, Probing Broccoli's Benefits for Prostate Cancer, Sci. Transl. Med. 1, 1ec4 (2009).

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