Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the androgen-independent growth of prostate cancer cells

Abstract

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.