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Research Paper|Volume 14, Issue 13|pp 5464—5477

Curcumin analogue BDDD-721 exhibits more potent anticancer effects than curcumin on medulloblastoma by targeting Shh/Gli1 signaling pathway

Weiyi Gong1, Wenxuan Zhao1, Gang Liu2, Lei Shi1, Xia Zhao3
  • 1Department of Neurosurgery, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Suzhou 215300, China
  • 2Department of Gastrointestinal Surgery, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Suzhou 215300, China
  • 3Department of Oncology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng 224006, China
* Equal contribution
Received: March 17, 2022Accepted: June 27, 2022Published: July 6, 2022
https://doi.org/10.18632/aging.204161

Copyright: © 2022 Gong 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

Medulloblastoma (MB) is a malignant tumor in the fourth ventricle of children. The clinical treatment is mainly surgical resection combined with radiotherapy and chemotherapy, but the curative effect is not ideal, and the 3-year survival rate is very low. Previous study confirmed that curcumin attenuated the proliferation of medulloblastoma both in vitro and in vivo. In present study, we found a curcumin analogue named BDDD-721, exhibited more potent anti-tumor activity than curcumin. Compared with curcumin, BDDD-721 more effectively inhibited the proliferation, migration, invasion, and increased apoptosis of medulloblastoma cells. Furthermore, BDDD-721 treatment led to activation of glioma-associated oncogene homolog (Gli), reduced expression of Shh and its downstream target Smo, Gli1 and Ptch1. In addition, SAG (Shh signaling pathway agonist) antagonized the pro-apoptotic effects of BDDD-721 on medulloblastomas as confirmed by CCK8 assays and flow cytometry; while cyclopamine (Shh signaling pathway inhibitor) enhanced its effects on medulloblastomas. In conclusion, these results indicate that curcumin analogue BDDD-721 has more potent anticancer effects than curcumin on medulloblastomas by targeting Shh/Gli1 signaling pathway.