Dataset Information

AKT Inhibitor SC66 Inhibits Proliferation and Induces Apoptosis in Human Glioblastoma Through Down-Regulating AKT/?-Catenin Pathway.

ABSTRACT: Glioblastoma multiforme (GBM) is the most common intracranial malignancy in adults with the highest degree of malignancy and mortality. Due to its nature of diffuse invasiveness and high migration, GBM lacks an effective treatment strategy and is associated with poor prognosis. SC66 is a novel AKT inhibitor that has been reported to exert antiproliferative activity in many types of cancer cells. However, it remains unclear whether SC66 has antitumor effects in GBM. In this study, we found SC66 obviously suppressed U87 and U251 cell proliferation and EMT- mediated cell migration and invasion. Moreover, SC66 induced GBM cells apoptosis and arrested cell cycle in G0/G1 phase. Furthermore, SC66 also downregulated AKT signaling pathway in a concentration dependent manner. We also found the level of ?-catenin nuclear translocation was prominently downregulated after SC66 treatment. Meanwhile, TCF/LEF luciferase report assay indicated that the activity of TCF/LEF was remarkably suppressed. Elevating ?-catenin activity by using IM12 rescued SC66 inhibition-mediated GBM cell proliferation and metastasis. In addition, SC66 showed significantly suppressed the tumorigenicity compared to the control group in the xenograft mouse model. In conclusion, our study demonstrated that SC66 exerts prominently antitumor efficiency in GBM cells in vivo and in vitro by downregulated AKT/?-catenin pathway.

SUBMITTER: Gao L

PROVIDER: S-EPMC7411127 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AKT Inhibitor SC66 Inhibits Proliferation and Induces Apoptosis in Human Glioblastoma Through Down-Regulating AKT/β-Catenin Pathway.

Gao Lun L Liu Junhui J Xu Pengfei P Deng Gang G Liu Baohui B Yuan Fanen F Tan Yinqiu Y Sun Qian Q Xu Yang Y Zhang Huikai H Qi Yangzhi Y Han Shoumeng S Yang Kun K Geng Rongxin R Jiang Hongxiang H Chen Qianxue Q

Frontiers in pharmacology 20200731

Glioblastoma multiforme (GBM) is the most common intracranial malignancy in adults with the highest degree of malignancy and mortality. Due to its nature of diffuse invasiveness and high migration, GBM lacks an effective treatment strategy and is associated with poor prognosis. SC66 is a novel AKT inhibitor that has been reported to exert antiproliferative activity in many types of cancer cells. However, it remains unclear whether SC66 has antitumor effects in GBM. In this study, we found SC66 o ...[more]

PMID: 32848734

Similar Datasets

Project description:BackgroundIcaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway.MethodsReal-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting.ResultsOur results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis.ConclusionOur findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

Dataset Information

AKT Inhibitor SC66 Inhibits Proliferation and Induces Apoptosis in Human Glioblastoma Through Down-Regulating AKT/?-Catenin Pathway.

Publications

AKT Inhibitor SC66 Inhibits Proliferation and Induces Apoptosis in Human Glioblastoma Through Down-Regulating AKT/β-Catenin Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets