Belal M Ali, Hanan S El-Abhar, Dalaal M Abdallah, Ghada Mohamed, Marwa Sharaky, Samia A. Shouman, Marwa Kamel
{"title":"The Enzalutamide and EPI-001 modulate cell proliferation and metastasis markers in T47D by targeting AR/ARV7","authors":"Belal M Ali, Hanan S El-Abhar, Dalaal M Abdallah, Ghada Mohamed, Marwa Sharaky, Samia A. Shouman, Marwa Kamel","doi":"10.22146/ijp.7416","DOIUrl":null,"url":null,"abstract":"Androgen receptor (AR) and its splicing variant 7 (ARv7) play vital roles in the pathobiology of breast cancer (BC) but their role in the estrogen receptor-positive (ER+) type is controversial. Hence, we studied the influence of the blockers of AR (Enzalutamide) and ARv7 (EPI-001) on tumorigenesis processes using T47D, an ER+ BC cell line. Several techniques were employed: Sulphorhodamine assay (SRB), Flow cytometry, Immunostaining, Scratch wound healing assay, Enzyme Linked Immunosorbent assay (ELISA), and Western blot. Mechanistically, the drugs successfully arrested the cell cycle at S-phase and downregulated the protein expression of cyclins A, E, & C. Additionally, they inhibited the cell proliferation stimulator nuclear factor kappa B (NF-ĸB), whereas only EPI-001 reduced the cell regulatory marker c-Myc. They also opposed the endothelial-to-mesenchymal transition (EMT) process, by boosting the epithelial marker E-cadherin and reducing the protein expression of the mesenchymal marker fibronectin. Their anti-metastatic potential was evidenced by the hindrance of cell migration using the wound healing assay and further confirmed by the downregulation of metalloproteinase (MMP) 2 and 9 protein expression, and protein content of Rho kinase (ROCK)1 and 2. Besides, by downregulating the protein expression of vascular endothelial growth factor (VEGF) the drugs point to their anti-angiogenic aptitude. In conclusion, this in-vitro study highlights the importance of targeting AR/ARv7 using Enzalutamide and EPI-001 in decreasing proliferation cell markers, EMT, and metastasis in ER+ BC cells, findings that may have great impact in the treatment of ER+ BC.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"INDONESIAN JOURNAL OF PHARMACY","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22146/ijp.7416","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Androgen receptor (AR) and its splicing variant 7 (ARv7) play vital roles in the pathobiology of breast cancer (BC) but their role in the estrogen receptor-positive (ER+) type is controversial. Hence, we studied the influence of the blockers of AR (Enzalutamide) and ARv7 (EPI-001) on tumorigenesis processes using T47D, an ER+ BC cell line. Several techniques were employed: Sulphorhodamine assay (SRB), Flow cytometry, Immunostaining, Scratch wound healing assay, Enzyme Linked Immunosorbent assay (ELISA), and Western blot. Mechanistically, the drugs successfully arrested the cell cycle at S-phase and downregulated the protein expression of cyclins A, E, & C. Additionally, they inhibited the cell proliferation stimulator nuclear factor kappa B (NF-ĸB), whereas only EPI-001 reduced the cell regulatory marker c-Myc. They also opposed the endothelial-to-mesenchymal transition (EMT) process, by boosting the epithelial marker E-cadherin and reducing the protein expression of the mesenchymal marker fibronectin. Their anti-metastatic potential was evidenced by the hindrance of cell migration using the wound healing assay and further confirmed by the downregulation of metalloproteinase (MMP) 2 and 9 protein expression, and protein content of Rho kinase (ROCK)1 and 2. Besides, by downregulating the protein expression of vascular endothelial growth factor (VEGF) the drugs point to their anti-angiogenic aptitude. In conclusion, this in-vitro study highlights the importance of targeting AR/ARv7 using Enzalutamide and EPI-001 in decreasing proliferation cell markers, EMT, and metastasis in ER+ BC cells, findings that may have great impact in the treatment of ER+ BC.
期刊介绍:
The journal had been established in 1972, and online publication was begun in 2008. Since 2012, the journal has been published in English by Faculty of Pharmacy Universitas Gadjah Mada (UGM) Yogyakarta Indonesia in collaboration with IAI (Ikatan Apoteker Indonesia or Indonesian Pharmacist Association) and only receives manuscripts in English. Indonesian Journal of Pharmacy is Accredited by Directorate General of Higher Education. The journal includes various fields of pharmaceuticals sciences such as: -Pharmacology and Toxicology -Pharmacokinetics -Community and Clinical Pharmacy -Pharmaceutical Chemistry -Pharmaceutical Biology -Pharmaceutics -Pharmaceutical Technology -Biopharmaceutics -Pharmaceutical Microbiology and Biotechnology -Alternative medicines.