Oridonin interrupts cellular bioenergetics to suppress glioma cell growth by down‐regulating PCK2

Abstract

We aim to evaluate the tumor metabolic suppressive activity of Oridonin (extract of Rabdosia rubescens) in glioma and elucidate its potential mechanism. Effects of Oridonin on U251/U87 cells were determined by CCK8, RTCA, colony formation, flow cytometry, wound healing, and Transwell assay. Xenograft tumor model to evaluate the effect of Oridonin on glioma cells in vivo. Cellular bioenergetics were measured by Seahorse. RNA-seq was performed to screen potential biological pathways in Oridonin treated cells. Bioinformatics analysis of PCK2 in glioma was performed based on TCGA/CGGA. Endogenous PCK2 was knocked-down by lentivirus packaged shRNA. We found Oridonin significantly inhibited cell growth in U251/U87 in vitro and in vivo. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were decreased in Oridonin-treated U251/U87 cells. Oridonin treatment led to PCK2 down-regulation. Additionally, PCK2 was up-regulated in higher grade glioma and correlated with poor outcomes. Furthermore, PCK2 depletion significantly inhibited cell growth and decreased OCR/ECAR in U251/U87 which coincided with the effects of Oridonin. Therefore, we evaluated the potent anti-tumor property of Oridonin in glioma. Importantly, we demonstrated that PCK2 might be a novel target of Oridonin on glioma by inducing energy crisis and increasing oxidative stress.

Hederagenin suppresses glioma cell biological activities via Nur77 in vitro study

“…Although symptoms of patients can, thus, be improved in a short time, it is apt to recur due to residual diseases; and, the corresponding prognosis is also rather poor (Li et al, 2016). In recent years, a variety of natural products have shown good effects in the prevention and treatment of glioma (Cao et al, 2017; Lin et al, 2021; Park et al, 2018). Hederagenin (Hed) belongs to triterpenoid acids, which are abundant in ivy leaves and have a wide range of biological activities (Rodríguez‐Hernández et al, 2015).…”