Research Paper Volume 12, Issue 23 pp 23795—23807
Demethoxycurcumin analogue DMC-BH exhibits potent anticancer effects on orthotopic glioblastomas
- 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 City First People's Hospital, Yancheng 224000, P. R. China
- 3 Department of Neurosurgery, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210029, P.R. China
Received: May 4, 2020 Accepted: July 30, 2020 Published: November 18, 2020
https://doi.org/10.18632/aging.103981How to Cite
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
Demethoxycurcumin (DMC) has anti-glioma effects in vitro and in subcutaneous xenotransplanted tumors. Our previous study confirmed that the molecule also has mild anti-glioma effects on orthotopic glioblastomas in vivo. In this study, we found that DMC-BH, a DMC analogue, exhibited more potent in vitro and in vivo activities than did DMC. DMC-BH was cytotoxic against various glioma cells including SHG-44, C6, U251, U87, A172 and primary glioma cells. DMC-BH activity was characterized by low acute toxicity and an appropriate pharmacokinetic profile. We evaluated the anti-tumor effects of DMC-BH in an ectopic xenograft model, an orthotopic glioblastoma xenograft model and a patient-derived tumor xenograft (PDTX) model. DMC-BH exhibited potent anti-tumor activity in both the ectopic xenograft and PDTX models. Indeed, bioluminescence measurements showed that DMC-BH exerted a significantly greater anti-tumor effect on orthotopic glioma growth than DMC. Immunohistochemical analysis revealed that DMC-BH inhibited expression of Ki67 and increased the incidence of TUNEL-positive cells. Western blotting showed that DMC-BH significantly decreased p-Akt and p-mTOR expression in orthotopic glioma tissues. These results suggest that the DMC analogue DMC-BH has potent anti-tumor properties that warrant further study.