SINE Compounds Inhibit Expression of XPO-1 and Shows Antitumor Properties in Prostate Cancer Models
December 9, 2015| |
Increased expression of Chromosome Region Maintenance(CRM-1)/exportin-1 (XPO-1) has been correlated with poor prognosis in aggressive tumors, making it an interesting therapeutic target. Selective Inhibitor of Nuclear Export (SINE) compounds bind to XPO-1 and block its ability to export cargo proteins. The team led by Giovanni Luca Gravina of the University of L'Aquila in Italy investigated the effects of a new class of SINE compounds in models of prostate cancer.
The team evaluated the expression of XPO-1 in human prostate cancer tissues and cell lines. Then, six different SINE compounds were tested on prostate cancer cells representing distinct progression states and genotypes. Among the six, two SINE candidates for clinical trials, KPT-251 and KPT-330, were then tested in three cell models of aggressive prostate cancer engrafted in male mice.
XPO-1 was found to be overexpressed in prostate cancer compared to normal tissues. SINE compounds inhibited proliferation and promoted apoptosis of the tumor cells,but did not affect non-tumor prostate epithelial cells. Oral administration of KPT-251 and KPT-330 in tumor-bearing nude mice reduced tumor cell proliferation, angiogenesis and induced apoptosis.
For more information, read the article in BMC Cancer.
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