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.

中文翻译：

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异硫氰酸苯乙酯与二苯甲酰甲烷联用可抑制雄激素非依赖性前列腺癌细胞的生长

异硫氰酸苯乙基酯（PEITC）是在某些十字花科蔬菜中发现的天然化合物。二苯甲酰甲烷（DBM）是甘草的次要成分。两种化合物均已显示出抗癌活性。在本研究中，我们确定了PEITC和DBM单独或组合对体外培养的人类前列腺癌细胞的雄激素非依赖性生长的影响和严重的联合免疫缺陷（SCID）小鼠的前列腺VCaP异种移植肿瘤。在培养的前列腺癌细胞中，PEITC和DBM的组合比单独使用任何一种化合物对抑制生长和诱导凋亡具有更强的作用。该组合还强烈抑制了VCaP细胞中的细胞迁移和肿瘤球的形成。机理研究表明，PEITC和DBM对生长抑制和凋亡的联合作用与抑制核因子κB（NF-κB）以及降低survivin和磷酸化Akt（pAkt）有关。在体内在一项研究中，对带有VCaP肿瘤的SCID小鼠进行了手术cast割，并用PEITC和/或DBM治疗。PEITC和DBM联合治疗可强烈抑制雄激素依赖性VCaP前列腺肿瘤向雄激素非依赖性的发展。我们的结果表明，联合使用DBM和PEITC可能是抑制/延迟前列腺癌发展为雄激素非依赖性的有效策略。