Theabrownin Induces Cell Apoptosis and Cell Cycle Arrest of Oligodendroglioma and Astrocytoma in Different Pathways.

J Y Fu,L Huang,J Zhang,R Y Mei,X F Zhao,M Y Wu,H P Tao,X J Chen,A F Yang,C X Jiang

doi:10.3389/fphar.2021.664003

J Y Fu, L Huang + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2021.664003

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Abstract

Theabrownin (TB), a natural compound present in the fresh leaves of green tea, is a potential antitumor agent. However, so far whether and how TB affects glioma is unclear. In this study, we investigated the effect of TB on astroglioma and oligodendroglioma cells. Surprisingly, TB significantly reduced the viabilities of HOG and U251 cells in a dose-dependent manner, which was accompanied by the upregulation of active-Casp-3, Bax, and PTEN; meanwhile, the antiapoptotic gene Bcl-2 was downregulated. In addition, TB treatment induced cell cycle arrest at the G1 and G2/M phases in HOG and U251 cells, respectively. TB treatment caused the downregulating of c-myc, cyclin D, CDK2, and CDK4 and upregulating of p21 and p27 in the HOG cell, while TB increased P53, p21, and p27 levels and decreased the levels of cell cycle regulator proteins such as CDK and cyclin A/B in the U251 cells. Therefore, the c-myc- and P53-related mechanisms were proposed for cell cycle arrest in these two glioma cell lines, respectively. Overall, our findings indicated that TB could be a novel candidate drug for the treatment of gliomas.

Highlights

Gliomas are specialized tumors arising from glial cells in the central nervous system (CNS), which can be divided into astrogliomas, oligodendrogliomas, and mixed oligoastrocytomas (Dolecek et al, 2012)
We found that TB significantly reduced the viabilities of HOG and U251 cells in a dose-dependent manner and induced cell cycle arrest at G1 and G2/M phases in HOG and U251 cells, respectively
We found that TB treatment caused an obvious inhibition of the cell survival rate of four glioma cells at various concentrations

Summary

Introduction

Gliomas are specialized tumors arising from glial cells in the central nervous system (CNS), which can be divided into astrogliomas, oligodendrogliomas, and mixed oligoastrocytomas (Dolecek et al, 2012). These gliomas are classified into different grades based on the growth rates: grade I tumors such as pilocytic astrocytomas and more common infiltrating gliomas; grade II oligodendrogliomas and astrocytomas; grade III anaplastic oligodendrogliomas, anaplastic astrocytomas, and anaplastic oligoastrocytomas; and grade IV glioblastomas (GBM). The high fatality rates and low survival rates of glioma make it one of the deadliest and incurable cancers (Bray et al, 2018). The widely used radiotherapy and chemotherapy have some limitations in cancer chemotherapy including the high cost of treatment (Penny and Wallace, 2015), multidrug resistance

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