Abscisic Acid-Induced Autophagy Selectively via MAPK/JNK Signalling Pathway in Glioblastoma

Nan Zhou,Zixuan Wei,Zengxin Qi,Liang Chen

doi:10.1007/s10571-020-00888-1

Nan Zhou, Zixuan Wei + Show 2 more

Open Access

https://doi.org/10.1007/s10571-020-00888-1

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Abstract

As a widely known plant hormone, Abscisic acid plays an important role in the progress of planting cell and their stress response. Recently, we reported that ABA might play an anti-cancer role in glioma tissues. In the present study, the molecular mechanism of ABA anti-cancer was further explored in glioblastoma cells. By measuring LC3 puncta formation and conversion in glioblastoma cells, inhibiting the autophagic pathway, targeting the essential autophagic modulator beclin 1 with RNA interference, and analysing cellular morphology via transmission electron microscopy, we found that ABA-treated glioblastoma cells exhibited the features of autophagy. Specifically, ABA-induced autophagy in glioblastoma cells was mediated by the MAPK/JNK signalling pathway rather than the PI3K/AKT/mTOR axis. Moreover, the inhibition or knockdown of JNK specifically blocked ABA-induced autophagic cell death. ABA-induced autophagy was further confirmed in tumour-bearing mice and was accompanied by the inhibition of glioma growth in vivo. This report is the first to describe autophagy induced by ABA and mediated by the MAPK/JNK pathway in human cancer cells and tumour-bearing mice. These results may shed some light in new therapeutic strategies of glioma.

Highlights

As a plant hormone, Abscisic acid (ABA) has been readily found in fruits and vegetables that can be naturally supplied by the dietary intake (Wasilewska et al 2008)
We tested the impact of ABA on the endogenous conversion of light chain 3 (LC3)-I to LC3-II and beclin 1 based on Western blotting
The knockdown of ERK or p38 neither affected the number of autophagic vacuoles nor the expression levels of beclin 1 and LC3-II in U87 and A172 cells (S-Figs. 3 and 4). These results suggest that the MAPK/JNK signalling pathway is causally related to ABA-induced autophagic cell death in glioblastoma cell lines

Summary

Introduction

Abscisic acid (ABA) has been readily found in fruits and vegetables that can be naturally supplied by the dietary intake (Wasilewska et al 2008). ABA plays a significant part in the progress of planting cell and their stress response and its medicinal applications have recently attracted significant attention (Bassaganya-Riera et al 2010; Li et al 2011). On account of a series of pioneering studies, Bruzzone et al illustrated that ABA perform as a regulator between various cell functions, incorporate inflammatory. Malignant glioblastomas (GBMs) are the most common form of primary brain tumours and are associated with the highest mortality rate (Ostrom et al 2014). The standard treatment for GBMs is the surgical resection of the tumour followed by concurrent radiation therapy (IR) and chemotherapy with temozolomide (TMZ). Advancements in recent decades have not significantly increased the overall survival of patients with this disease, and it remains an intractable problem to discover

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