Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system.Due to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat BC.Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential.Herein,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular mechanism.We found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC cells.Besides,Ecn had no notable cytotoxicity towards human normal cells.We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells.Remarkably,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells.In summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling pathways.More meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.

Alantolactone inhibits proliferation,metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

Although there are many therapeutic strategies such as surgery and chemotherapy,the prognosis of osteosarcoma(OS)is still far from being satisfactory.It is urgent to develop more effective,tolerable and safe drugs for the treatment of OS.In the present study,we investigated the anti-OS activity of Alantolactone(ALT),a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium,and probed the possible mechanism involved.We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells.Then,we validated that ALT reduced migration,decreased invasion possibly through reversing epithelial mesenchymal transition(EMT)process and suppressing Matrix metalloproteinases(MMPs).Moreover,we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro.In addition,we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo.Mechanistically,ALT inhibited the activity of Wnt/β-catenin and p38,ERK1/2 and JNK Mitogen Activated Protein Kinases(MAPKs)signal pathway.Notably,the combination of ALT and Wnt/β-catenin inhibitor,as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation,migration and invasion of OS cells.Collectively,our results validate the ALT may inhibit proliferation,metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.