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].
PX-12 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Intestinal epithelial cells
1 µM
12 hours
To explore the inhibitory effect of PX-12 on TRX1, the results showed that PX-12 reversed the inhibitory effect of Nano AC on the NLRP3/Caspase-11/GSDMD signaling pathway
Int J Nanomedicine. 2024 Dec 31;19:14125-14141.
HCT-15
20 µM
16 hours
PX-12 reversed the upregulation of phosphorylated NF-κB, CAT, and SOD2 protein levels in HCT-15 cells and reversed ALDH1L2-mediated CRC radioresistance.
Br J Cancer. 2022 Sep;127(4):637-648.
HCT 116
20 µM
16 hours
PX-12 reversed the upregulation of phosphorylated NF-κB, CAT, and SOD2 protein levels in HCT 116 cells and reversed ALDH1L2-mediated CRC radioresistance.
Br J Cancer. 2022 Sep;127(4):637-648.
Human neutrophils
10 µM or 100 µM
16 hours
PX-12 inhibited thioredoxin function, increasing the sensitivity of fungal hyphae to both H2O2- and neutrophil-mediated killing.
J Clin Invest. 2012 Jul;122(7):2482-98.
Human aortic endothelial cells (HAECs)
1 µM
2 hours
Inhibiting TRX completely blunted the protective effect of silencing TXNIP
Genes Dis. 2020 Aug 31;9(3):753-765.
HT-29 cells
5 µM
24 hours
To investigate the effect of PX-12 on IL-6-induced nuclear translocation of Trx-1 and pSTAT3. Results showed that PX-12 treatment decreased nuclear expression of Trx-1 and pSTAT3 in HT-29 cells.
Theranostics. 2023 Aug 28;13(14):4730-4744.
LNCaP SB5
0.5 µM, 1.5 µM, 2.5 µM
72 hours
To evaluate the effect of PX-12 on the viability of CRPC cells, the results showed that PX-12 significantly reduced the viability of CRPC cells, and was more sensitive under CSS conditions.
Nat Commun. 2017 Oct 31;8(1):1204.
LNAI
0.5 µM, 1.5 µM, 2.5 µM
72 hours
To evaluate the effect of PX-12 on the viability of CRPC cells, the results showed that PX-12 significantly reduced the viability of CRPC cells, and was more sensitive under CSS conditions.
Nat Commun. 2017 Oct 31;8(1):1204.
22Rv1
0.5 µM, 1.5 µM, 2.5 µM
72 hours
To evaluate the effect of PX-12 on the viability of CRPC cells, the results showed that PX-12 significantly reduced the viability of CRPC cells, and was more sensitive under CSS conditions.
Nat Commun. 2017 Oct 31;8(1):1204.
C4-2b
0.5 µM, 1.5 µM, 2.5 µM
72 hours
To evaluate the effect of PX-12 on the viability of CRPC cells, the results showed that PX-12 significantly reduced the viability of CRPC cells, and was more sensitive under CSS conditions.
Nat Commun. 2017 Oct 31;8(1):1204.
PX-12 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c Nude mice
Xenograft colorectal cancer model
Intraperitoneal injection
12 mg/kg
Daily until the end of the experiment
PX-12 significantly inhibited tumor growth, and tumor weight decreased by ~90% following combined treatment with radiotherapy and PX-12, indicating its possible clinical application.
Br J Cancer. 2022 Sep;127(4):637-648.
Nu/Nu mice
Castration-resistant prostate cancer model
Intraperitoneal injection
12.5 mg/kg
5 times a week, lasting several weeks
To evaluate the effect of PX-12 on the growth of castration-resistant prostate cancer tumors, the results showed that PX-12 significantly inhibited tumor growth and led to complete tumor regression.
Nat Commun. 2017 Oct 31;8(1):1204.
C57BL/6 mice
AOM/DSS-induced colitis-associated cancer model
Tail vein injection
12.5 mg/kg
Daily administration during three recovery periods
To investigate the effect of PX-12 on the AOM/DSS-induced colitis-associated cancer model. Results showed that PX-12 significantly reduced tumor formation and suppressed nuclear expression of Trx-1 and pSTAT3.
Theranostics. 2023 Aug 28;13(14):4730-4744.
Mice
Fungal keratitis model
Topical application
3 mM
Twice, 6 hours apart
PX-12 significantly enhanced neutrophil-mediated fungal killing and reduced fungal growth.
United States, Arizona
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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
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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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