Tubeimoside-1 Inhibits Glioblastoma Growth, Migration, and Invasion via Inducing Ubiquitylation of MET.

Jiangjun Cao,Erhu Zhao,Zekun Wei,Juanli Ji,Qingzong Zhu,Bo Xu,Hongjuan Cui

doi:10.3390/cells8080774

Abstract

Tubeimoside-1 (TBMS1) is one of the extracts of rhizoma bolbostemmae, which has remarkable anti-cancer function in the treatment of esophagus and gastric cancer in traditional Chinese medicine. However the mechanisms of its anti-cancer function is remain unclear. In this study, we demonstrate that TBMS1 could inhibit cell growth and metastasis in glioblastoma. MET is a member of the receptor tyrosine kinase family, which amplifies frequently in various human cancers. As an important proto-oncogene, multiple inhibitors have been developed for the therapy of cancers. Here, we found TBMS1 could reduce/decrease the protein level of MET via increasing its Ubiquitination degradation. Therefore, TBMS1 is a promising compound for the treatment of glioblastoma and an inhibitor of MET.

Highlights

Rhizoma bolbostemmae is a kind of Chinese traditional medicinal materials, which is used therapeutically for Mammary carbuncles, scrofula, and phlegm nodes
We examined the effects of TBMS1 on glioblastoma cells, LN229 and U87 treated with different concentrations of TBMS1 (1, 5, 10, and 20 μM, dimethyl sulfoxide (DMSO) was used as control) for 24 h
MTT assay showed that glioblastoma cells treated with 1, 5, 10, and 20 μM TBMS1 showed sharp declines in the growth curve comparing to DMSO group (Figure 1c)

Summary

Introduction

Rhizoma bolbostemmae is a kind of Chinese traditional medicinal materials, which is used therapeutically for Mammary carbuncles, scrofula, and phlegm nodes. In Sichuan and Shanxi, rhizoma bolbostemae is regarded as an effective traditional Chinese herb for the treatment of esophagus and gastric cancer. Tubeimoside-1 (TBMS1) is the Chinese medicine monomer with a high yield (1.9%), water solubility, and stability extracted from the anti-cancer active ingredient saponin. Glioblastoma (GBM) is the most common subtype tumor among malignant gliomas. As a malignant tumor with high metastasis and recurrence, the prognoses of radiotherapy and chemotherapy are poor [1,2]. With the emergence of important target genes, targeting therapy has become a potential approach for the treatment of glioblastoma. Crizotinib, an ATP-competitive small molecule inhibitor of MET, and Onartuzumab, a monovalent monoclonal antibody that binds to the extracellular domain of the MET receptor, have achieved certain results in clinical treatment [3]

Methods

Results

Conclusion