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Hypoxia‐Selective Growth Inhibition of Cancer Cells by Furospinosulin‐1, a Furanosesterterpene Isolated from an Indonesian Marine Sponge
Author(s) -
Arai Masayoshi,
Kawachi Takashi,
Setiawan Andi,
Kobayashi Motomasa
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000302
Subject(s) - du145 , metastasis , angiogenesis , cancer cell , prostate cancer , cancer research , biology , growth inhibition , pharmacology , hypoxia (environmental) , cancer , chemistry , cell growth , biochemistry , lncap , genetics , organic chemistry , oxygen
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 μ M . Furospinosulin‐1 also demonstrated antitumor activity at 10–50 mg kg −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.