Paris saponin VII extracted from trillium tschonoskii suppresses proliferation and induces apoptosis of human colorectal cancer cells

Abstract

Ethnopharmacological relevanceSaponins of many herbs could inhibit the growth of colorectal cancer cells. In the study, we investigated the effects of Paris saponin Ⅶ (PSⅦ), and elucidated its mechanism in colorectal carcinoma cells and a xenograft mouse model. Materials and methodsHT-29 and HCT-116 cells were treated with different concentrations of PSⅦ (0–100 μM). The effects of PSⅦ on HCT-116 cells were assessed using a microarray. Then, apoptotic cells were detected by flow cytometric analysis and apoptosis related protein expression was evaluated by Western blot. A xenograft model of nude mice was used to assess the effect of PSⅦ in vivo. ResultsMTT assay showed the IC50 values of PSⅦ for growth inhibition of HT-29 and HCT-116 cells were 1.02 ± 0.05 μM and 3.50 ± 0.79 μM respectively. Edu assay demonstrated that PSⅦ effectively suppressed the growth of HT-29 and HCT-116 cells. Treatment with 0–3 μM PSⅦ not only triggered apoptosis, but also activated caspase-3 and caspase-9 of HT-29 and HCT-116 cells in a concentration dependent manner. In parallel to the alterations, Bax and Cyto-c expression increased while Bcl-2 decreased. In nude mice, PSⅦ reduced the tumor size and induced the apoptosis of tumor cells. PSVII could suppress IL-6-induced phosphorylation of STAT3 in vitro and blocked STAT3 phosphorylation in vivo. ConclusionOur results suggest that PSVII suppressed the activation of IL-6/STAT3 pathway, consequently suppressed the growth and proliferation and triggered the apoptosis of CRC cells. These findings indicate that PSⅦ might be an effective tumouristatic agent for the treatment of colorectal cancer.