Journal
CANCER LETTERS
Volume 420, Issue -, Pages 195-207Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.02.005
Keywords
Hh pathway inhibitor; Gli inhibitor; Natural product; C-21 steroid; Medulloblastoma; Acquired resistance
Categories
Funding
- National Natural Science Foundation of China [21472175]
- Zhejiang Provincial Natural Science Foundation [LY15H280001, LQ16H300002]
- Zhejiang Provincial Science and Technology Council [2017F10005, LGF18H310003]
- Zhejiang Provincial Medicinal Health Program [201472465, 2014KYA037]
- Zhejiang Provincial Education Council [Y201738521]
Ask authors/readers for more resources
Uncontrolled excessive activation of Hedgehog (Hh) signaling pathway is linked to a number of human malignant tumorigenesis. To obtain valuable Hh pathway inhibitors from natural product, in present study, a pair of novel epimers, Cynanbungeigenin C (CBC) and D (CBD) from the plant Cynanchum bungei Decne were chemically characterized by multiple spectroscopic data and chemical derivatization, and evaluated for their inhibition on Hh pathway. Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli. In addition, both eipmers significantly suppress Hh pathway-dependent Ptch(+/-); p53(-/-) medulloblastoma in vitro and in vivo. Furthermore, both CBC and CBD inhibited two Smo mutants induced Hh pathway activation, which suggested that they are potential compounds for the treatment of medulloblastoma with primary or acquired resistance to current Smo inhibitors. These results highlight the potential of CBC and CBD as effective lead compounds in the treatment of medulloblastoma and other Hh-dependent malignancy. (C) 2018 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available