Chelerythrine suppresses proliferation and metastasis of human prostate cancer cells via modulating MMP/TIMP/NF-κB system.

Abstract

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 10μM, 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.