4.6 Article

Anticarin β Inhibits Human Glioma Progression by Suppressing Cancer Stemness via STAT3

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.715673

Keywords

natural product; glioma; apoptosis; DNA damage; stemness

Categories

Funding

  1. National Natural Science Foundation of China [81903666]
  2. Science and Technology Department of Yunnan Province [202101AT070301, 202002AA100007, 2019ZF003]

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The study demonstrated that anticarin beta can effectively suppress proliferation and induce apoptosis in glioma cells, decrease stemness gene expression, induce DNA damage, and eventually lead to apoptosis by regulating oncogene expression. Overall, anticarin beta shows promising potential as an inhibitor for malignant glioma.
Glioma is the most common form of malignant brain cancer. It is very difficult to cure malignant glioma because of the presence of glioma stem cells, which are a barrier to cure, have high tumorigenesis, associated with drug resistance, and responsible for relapse by regulating stemness genes. In this study, our results demonstrated that anticarin beta, a natural compound from Antiaris toxicaria, can effectively and selectively suppress proliferation and cause apoptosis in glioma cells, which has an IC50 that is 100 times lower than that in mouse normal neural stem cells. Importantly, cell sphere formation assay and real time-quantitative analysis reveal that anticarin beta inhibits cancer stemness by modulating related stemness gene expression. Additionally, anticarin beta induces DNA damage to regulate the oncogene expression of signal transducer and activator of transcription 3 (STAT3), Akt, mitogen-activated protein kinases (MAPKs), and eventually leading to apoptosis. Furthermore, anticarin beta effectively inhibits glioma growth and prolongs the lifts pan of tumor-bearing mice without systemic toxicity in the orthotopic xenograft mice model. These results suggest that anticarin beta is a promising candidate inhibitor for malignant glioma.

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