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Strusi, Gabriele, Suelzu, Caterina M., Weldon, Shannon, Giffin, Jennifer, Münsterberg, Andrea E. 
ORCID: https://orcid.org/0000-0002-4577-4240 and Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370
(2023)
Combination of phenethyl isothiocyanate and dasatinib inhibits hepatocellular carcinoma metastatic potential through FAK/STAT3/Cadherin signalling and reduction of VEGF secretion.
Pharmaceutics, 15 (10).
ISSN 1999-4923
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Abstract
Cancerous cells are characterised by their ability to invade, metastasise, and induce angiogenesis. Tumour cells use various molecules that can be targeted to reverse these processes. Dasatinib, a potent Src inhibitor, has shown promising results in treating hepatocellular carcinoma (HCC) in vitro and in vivo. However, its effectiveness is limited by focal adhesion kinase (FAK) activation. Isothiocyanates, on the other hand, are phytochemicals with broad anticancer activity and FAK inhibition capabilities. This study evaluated the synergistic effect of dasatinib and phenethyl isothiocyanate (PEITC) on HCC. The combination was tested using various assays, including MTT, adhesion, scratch, Boyden chamber, chorioallantoic membrane (CAM), and yolk sac membrane (YSM) assays to evaluate the effect of the drug combination on HCC metastatic potential and angiogenesis in vitro and in vivo. The results showed that the combination inhibited the adhesion, migration, and invasion of HepG2 cells and reduced xenograft volume in the CAM assay. Additionally, the combination reduced angiogenesis in vitro, diminishing the growth of vessels in the tube formation assay. The inhibition of FAK/STAT3 signalling led to increased E-cadherin expression and reduced VEGF secretion, reducing HCC metastatic potential. Therefore, a combination of PEITC and dasatinib could be a potential therapeutic strategy for the treatment of HCC.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This research was funded by Cancer Prevention Research Trust London. |
| Uncontrolled Keywords: | combination therapy,peitc,dasatinib,oncology,cancer therapeutics,drug development,cam assay,vegf,fak,hcc,oncology,pharmaceutical science,sdg 3 - good health and well-being,3* ,/dk/atira/pure/subjectarea/asjc/3000/3003 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 28 Sep 2023 09:30 |
| Last Modified: | 09 Mar 2024 01:49 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/93122 |
| DOI: | 10.3390/pharmaceutics15102390 |
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