Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 May 13

PMID 37175205

Authors

Ya-Fang Liao

Hui-Jun Pan

Nuerziba Abudurezeke

Chun-Lu Yuan

Yan-Li Yuan

Shu-Da Zhao

Dan-Dan Zhang

Shuang Huang

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCβ), cellular cGMP, and phosphorylation of VASP. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated β-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded β-catenin expression. As β-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with β-catenin function through the activation of a PDE5/cGMP functional axis.

Citing Articles

The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment.

Liu Z, Cao Y, Guo X, Chen Z Molecules. 2023; 28(14).

PMID: 37513375 PMC: 10386027. DOI: 10.3390/molecules28145500.

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