Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important
gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from
L-cysteine by multiple
enzymes, including
cystathionine gamma-lyase,
cystathionine beta-synthase, and
3-mercaptopyruvate sulfurtransferase in combination with
cysteine aminotransferase.
Prostate cancer is a major health concern and no effective treatment for
prostate cancers is available. H2S has been shown to inhibit cell survival of
androgen-independent,
androgen-dependent, and
antiandrogen-resistant
prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including
sulfide salts,
diallyl disulfide,
diallyl trisulfide,
sulforaphane, and other polysulfides, also have been shown to inhibit
prostate cancer growth and
metastasis. The expression of H2S-producing
enzyme was reduced in both human
prostate cancer tissues and
prostate cancer cells.
Androgen receptor (AR) signaling is indispensable for the development of
castration resistant
prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to
antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in
prostate cancer and described the molecular alterations, which may bring this
gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for
prostate cancer.