Phenethyl isothiocyanate (
PEITC) is a naturally occurring compound found in some cruciferous vegetables.
Dibenzoylmethane (DBM) is a minor constituent of licorice. Both compounds have been shown to exert anticancer activities. In the present study, we determined the effects of
PEITC and DBM alone or in combination on
androgen-independent growth of human
prostate cancer cells cultured in vitro and prostate VCaP xenograft
tumors in severe combined immunodeficient (SCID) mice.
PEITC and DBM in combination had stronger effects on inhibiting the growth and inducing apoptosis than either compound alone in cultured
prostate cancer cells. The combination also strongly inhibited cell migration and the formation of tumorspheres in VCaP cells. Mechanistic studies showed that the combined effects of
PEITC and DBM on growth inhibition and apoptosis were associated with suppression of nuclear factor-κB (NF-κB), and a decrease in the levels of
survivin and phospho-Akt (pAkt). In the in vivo study, SCID mice bearing VCaP
tumors were surgically castrated and treated with
PEITC and/or DBM. Treatment with
PEITC and DBM in combination resulted in a strong inhibition of the progression of
androgen-dependent VCaP prostate
tumors to
androgen independence. Our results indicate that administration of DBM and
PEITC in combination may be an effective strategy for inhibiting/delaying the progression of
prostate cancer to
androgen independence.