Research Paper|Volume 12, Issue 14|pp 14718—14735

Demethoxycurcumin analogue DMC-BH inhibits orthotopic growth of glioma stem cells by targeting JNK/ERK signaling

Lei Shi¹, Guan Sun², Haifeng Zhu³

¹Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, P.R.China
²Department of Neurosurgery, The Fourth Affiliated Hospital of Nantong University, Yancheng No.1 People's Hospital, Yancheng 224000, P. R. China
³Department of Neurosurgery, Funing People’s Hospital, Funing 224400, P.R.China

* Equal contribution

Received: November 10, 2019Accepted: May 20, 2020Published: July 24, 2020

Copyright: © 2020 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Glioma stem cells (GSCs) play an important role in glioblastoma resistance to conventional therapies and disease recurrence. Here, we assessed the therapeutic effect of a demethoxycurcumin analogue, DMC-BH, on GSCs, and investigated the underlying mechanisms. Our in vitro data demonstrate that DMC-BH inhibits GSC proliferation, and induces apoptosis and autophagy in GSCs. In addition, our results show that DMC-BH effectively crosses the blood-brain barrier to inhibit the growth of intracranial GSC tumors in vivo. DMC-BH significantly increased phosphorylation levels of JNK, ERK and c-Jun in GSCs. Inhibition of JNK and ERK activities reversed the pro-apoptotic effect of DMC-BH in GSCs, indicating that the DMC-BH-induced apoptosis in GSCs is mediated via the JNK/ERK signaling pathway. These results suggest that DMC-BH could potentially serve as a effective therapy against GSCs that acts by targeting the JNK/ERK signaling pathway.