Chelerythrine is a natural benzo[c]phenanthridine alkaloid found in many herbs and displays a wide range of antitumor activities. Here, the present study tested their effects on prostate cancer cells. The addition of chelerythrine can significantly inhibit the proliferation of androgen-independent prostate cancer DU145 and PC-3 cells at the concentration of 5 and 10 μM, but not on androgen-dependent prostate cancer LNCaP cells as well as normal prostate epithelial cell line PrEC cells. Wound migration and transwell invasion assay showed the similar inhibitory effect of chelerythrine on the migration and invasion of DU145 and PC-3 cells in the same condition. Western blot analysis further confirmed that chelerythrine not only dramatically decreased MMP-2, MMP-9, and uPA protein expression, but also augmented the expression of their endogenous inhibitors (TIMP-1 and TIMP-2) and plasminogen activator inhibitors (PAI-1 and PAI-2) in both cancer cells. Meanwhile, NF-κB and AP-1 transcription factors were all suppressed as evidenced by the decline of p-p65, c-Fos, and c-Jun protein expression in both cells. Taken together, these findings suggested that chelerythrine could reduce the metastasis of androgen-independent prostate cancer cells via modulation of MMP/TIMP system and inactivation of NF-κB pathway.

白屈菜红碱是一种天然的苯并[c]菲啶生物碱，存在于许多草药中，具有广泛的抗肿瘤活性。在这里，本研究测试了它们对前列腺癌细胞的作用。白屈菜红碱的添加可以在5和10μM的浓度下显着抑制雄激素非依赖性前列腺癌DU145和PC-3细胞的增殖，但对雄激素非依赖性前列腺癌LNCaP细胞以及正常的前列腺上皮细胞系PrEC细胞没有抑制作用。伤口迁移和transwell侵袭试验显示白屈菜红碱在相同条件下对DU145和PC-3细胞的迁移和侵袭具有相似的抑制作用。Western印迹分析进一步证实白屈菜红碱不仅可以显着降低MMP-2，MMP-9和uPA蛋白的表达，而且还增加了它们的内源性抑制剂（TIMP-1和TIMP-2）和纤溶酶原激活剂抑制剂（PAI-1和PAI-2）在两种癌细胞中的表达。同时，NF-κB和AP-1转录因子均被抑制，p-p65，c-Fos和c-Jun蛋白在两个细胞中的表达均下降。综上所述，这些发现表明白屈菜红碱可以通过调节MMP / TIMP系统和使NF-κB通路失活来减少非雄激素依赖性前列腺癌细胞的转移。