Home
Resources
Publications
PNU-74654 Enhances the Antiproliferative Effects of 5-FU in Breast Cancer and Antagonizes Thrombin-Induced Cell Growth via the Wnt Pathway

PNU-74654 Enhances the Antiproliferative Effects of 5-FU in Breast Cancer and Antagonizes Thrombin-Induced Cell Growth via the Wnt Pathway

Farzad Rahmani, Forouzan Amerizadeh, Seyed Mahdi Hassanian, Milad Hashemzehi, Seyedeh-Najibeh Nasiri, Hamid Fiuji, Gordon A Ferns, Majid Khazaei, Amir Avan

J Cell Physiol. 2019 Aug;234(8):14123-14132.

PMID: 30633353

Abstract:

The Wnt/β-catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential-therapeutic target. We have investigated the effects of PNU-74654 in breast cancer, as a Wnt/β-catenin inhibitor, either alone or in combination with fluorouracil (5-FU). PNU-74654 suppressed cell growth at an IC 50 of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU. These data show the ability of PNU-74654 to specifically target Wnt pathway, interfere with cell proliferation, induce-apoptosis, reduce-migration, and synergistically interact with 5-FU, supporting further studies on this novel therapeutic-approach for breast cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP113906277	PNU-74654		113906-27-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: