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

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 atten...

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Detalles Bibliográficos
Autores principales: Gong, Weiyi, Zhao, Wenxuan, Liu, Gang, Shi, Lei, Zhao, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320555/
https://www.ncbi.nlm.nih.gov/pubmed/35802536
http://dx.doi.org/10.18632/aging.204161
Descripción
Sumario: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.