The extract of Paris polyphylla exerts apoptotic induction and synergic antiproliferative effect with anticancer drugs in SMMC-7721 human liver cancer cells

Paris polyphylla is a famous traditional Chinese medicine with anti-inflammatory and hematischesis properties and has been shown recently to possess anticancer activities. However, the molecular mechanism underlying the anticancer effect of the herb is poorly understood. In this study, its ability to induce apoptosis and exert a synergistic antiproliferative effect by a combination with 5-fluorouracil (5-Fu) and Oxaliplatin (Oxa) were investigated in human SMMC-7721 liver cancer cells. Our findings have shown that the 95% ethanol extract of Paris polyphylla (PPE) inhibited the proliferation of SMMC-7721 cells dose- and time-dependently, as shown by loss of cell viability. The apoptotic induction was determined by Annexin-V/PI double staining assay, apoptotic body and swollen mitochondria observed under electron microscope, and breakdown of mitochondrial membrane potentials detected by JC-1 staining. Moreover, apoptosis in the SMMC-7721 cells was accompanied by S phase cell cycle arrest, the activation of pro-caspase 3, and a marked increase in Bax/Bcl-2 ratios due to upregulation of Bax and downregulation of Bcl-2 proteins expression by western blotting. In addition, we have observed that PPE increased the inhibitory effect of 5-Fu and Oxa on the proliferation of SMMC-7721 cells in vitro using Media-effect analysis. This combination regimen was more potent than either agent alone. Furthermore, the mRNA levels of thymidylate synthase (TS) and human excision repair cross-complementing (ERCC1) were suppressed when incubation with PPE, indicating that the effect of PPE on TS and ERCC1 mRNA levels at least partly caused the synergic effect. Overall, these results offer a potential mechanism for PPE-induced apoptosis and its synergic effect with anticarcinogenic drugs in SMMC-7721 cancer cells and indicate Paris polyphylla as a promising herb for chemoprevention and chemotherapy of hepotoma.