Polyphyllin G induce apoptosis and autophagy in human nasopharyngeal cancer cells by modulation of AKT and mitogen-activated protein kinase pathways in vitro and in vivo

Abstract

Polyphyllin G (also call polyphyllin VII), extract from rhizomes of Paris yunnanensis Franch, has been demonstrated to have strong anticancer activities in a wide variety of human cancer cell lines. Previous studies found that Polyphyllin G induced apoptotic cell death in human hepatoblastoma cancer and lung cancer cells. However, the underlying mechanisms of autophagy in human nasopharyngeal carcinoma (NPC) remain unclear. In this study, Polyphyllin G can potently induced apoptosis dependent on the activations of caspase-8, -3, and -9 and the changes of Bcl-2, Bcl-xL and Bax protein expression in different human NPC cell lines (HONE-1 and NPC-039). The amount of both LC3-II and Beclin-1 was intriguingly increased suggest that autophagy was induced in Polyphyllin G-treated NPC cells. To further clarify whether Polyphyllin G-induced apoptosis and autophagy depended on AKT/ERK/JNK/p38 MAPK signaling pathways, cells were combined treated with AKT inhibitor (LY294002), ERK1/2 inhibitor (U0126), p38 MAPK inhibitor (SB203580), or JNK inhibitor (SP600125). These results demonstrated that Polyphyllin G induced apoptosis in NPC cells through activation of ERK, while AKT, p38 MAPK and JNK were responsible for Polyphyllin G-induced autophagy. Finally, an administration of Polyphyllin G effectively suppressed the tumor growth in the NPC carcinoma xenograft model in vivo. In conclusion, our results reveal that Polyphyllin G inhibits cell viability and induces apoptosis and autophagy in NPC cancer cells, suggesting that Polyphyllin G is an attractive candidate for tumor therapies. Polyphyllin G may promise candidate for development of antitumor drugs targeting nasopharyngeal carcinoma.

Paris saponin VII enhanced the sensitivity of HepG2/ADR cells to ADR via modulation of PI3K/AKT/MAPK signaling pathway

“…Zhang et al found that PS VII inhibited MAPK signaling pathway to have its strong antiinflammatory effects on different in vitro and in vivo models . Moreover, PS VII was found able to induce apoptosis of nasopharyngeal carcinoma cells by activating ERK, while AKT and p38 MAPK were responsible for PS VII‐induced autophagy . Not surprisingly, PS VII‐treated HepG2/ADR cells in this work also exhibited the reduced p‐PI3K, p‐AKT, and p‐p38 in a concentration‐dependent manner, suggesting that PS VII may inhibit PI3K/AKT/MAPK signaling pathway to reverse the drug resistance of HCC HepG2/ADR cells to ADR.…”

Quinalizarin Induces Apoptosis through Reactive Oxygen Species (ROS)-Mediated Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathways in Colorectal Cancer Cells

“…The MAPK signaling pathway is known as a stress-activated kinase, and it participates in the regulation of cellular responses [ 32 ]. MAPK has been shown to promote drug resistance and the regulation of p53, and Bcl-2 may activate MAPK to induce apoptosis [ 33 ]. STAT3 is correlated with poor prognosis in cancer patients and has been regarded as a specific target of cancer treatment [ 34 ].…”

Coronarin D induces apoptotic cell death through the JNK pathway in human hepatocellular carcinoma

“…As previously described, cells were implanted onto six‐well overnight and then treated with different doses of coronarin D for 24 h. Cells were harvested and suspended in PBS (2% BSA), and then incubated with Muse Annexin V & Dead Cell reagent (EMD Millipore, Billerica, Massachusetts) for 20 min at room temperature in dark. Samples were analyzed by Muse Cell Analyzer flow cytometry and processed data by Muse Cell Soft V1.4.0.0 Analyzer Assays.…”