The high expression of redox protein thioredoxin-1 (Trx-1) has been reported in many human cancers, which increases the resistance of cells to apoptosis and induces the production of angiogenic factors. PX-12 is a potent inhibitor of Trx-1. It inhibits the growth of HT-29 and MCF-7 cells with IC50 values of 2.9 2.0μM and 1.9 0.8μM, respectively. The exposure of MCF-7 cells with PX-12 during hypoxia dose-dependently reduced the protein expression of hypoxia-inducible factor-1 (HIF-1) with an IC50 of 7.2 0.9μM. PX-12 also resulted in significant inhibition of hypoxia-induced HIF-1 trans-activating activity in MCF-7 cells with an IC50 of 11.5 ± 1.1μM. The hypoxia-stimulated formation of vascular endothelial growth factor (VEGF) was decreased by PX-12 treatment in both MCF-7 and HT-29 cells with IC50 values of 10.4 ± 2.5 and 10.1 ± 2.2μM, respectively. In mice with MCF-7 tumor xenografts, i.p. administration of 12mg/kg PX-12 significantly decreased VEGF protein expression and microvessel density 24 hours after the injection as compared with untreated animals[3]. PX-12 at 0.1-100μM inhibits the thioredoxin system mediated gp120 reduction in a concentration dependent manner, thus showing anti-HIV-1 activity in TZM-bl cells[4].
作用机制
PX-12 potently inhibits Trx-1 via the irreversible thioalkylation of the Cys73 residue, leading to the inhibition of Trx-dependent cell growth[3].
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TGen Clinical Research Services at Scottsdale Healthcare
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Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Texas
Tyler Cancer Center
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TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
Arizona Cancer Center, University of Arizona
Tucson, Arizona, United States, 85724
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030 收起 <<
United States, Arizona
... 展开 >>
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, South Carolina
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Texas
Tyler Cancer Center
Tyler, Texas, United States, 75702 收起 <<
United States, Arizona
... 展开 >>
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
Arizona Cancer Center, University of Arizona
Tucson, Arizona, United States, 85724
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030 收起 <<
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