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
- 1 Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, P.R.China
- 2 Department of Neurosurgery, The Fourth Affiliated Hospital of Nantong University, Yancheng No.1 People's Hospital, Yancheng 224000, P. R. China
- 3 Department of Neurosurgery, Funing People’s Hospital, Funing 224400, P.R.China
Received: November 10, 2019 Accepted: May 20, 2020 Published: July 24, 2020
https://doi.org/10.18632/aging.103531How to Cite
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.