期刊
CHEMMEDCHEM
卷 5, 期 11, 页码 1919-1926出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201000302
关键词
cancer; furospinosulin-1; hypoxia; natural products; terpenoids
资金
- Hoh-ansha Foundation
- Uehara Memorial Foundation,
- Naito Foundation
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
It is generally accepted that cancer cells, which have adapted to the hypoxic environments in tumor tissues, aggravate cancer pathology by promoting tumor growth, angiogenesis, metastasis, and drug resistance. Therefore, compounds that selectively inhibit the growth of tumor cells in hypoxic environments are expected to provide new leads for promising anticancer drugs. Furospinosulin-1, a marine-sponge-derived furanosesterterpene, exhibited selective antiproliferative activity against DU145 human prostate cancer cells under hypoxic conditions in concentrations ranging from 1 to 100 mm. Furospinosulin-1 also demonstrated antitumor activity at 10-50 mgkg(-1) oral administration in a mouse model inoculated with sarcoma S180 cells. Mechanistic analysis revealed that furospinosulin-1 suppresses transcription of the insulin-like growth factor-2 gene (IGF-2), which is selectively induced under hypoxic conditions through prevention of the binding of nuclear proteins to the Sp1 consensus sequence in the IGF-2 promoter region.
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