Romanian Society of Pharmaceutical Sciences
 

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EXPLORING THE REPURPOSING OF CARDIOTONIC GLYCOSIDES DIGOXIN AND DIGITOXIN ON MIA PaCa-2 PANCREATIC CANCER CELL LINE AS ALTERNATIVE TREATMENTS

DANIEL FLORIN PANCU 1#, ALINA TĂNASE 2# , MIRELA VOICU 1* , IASMINA-ALEXANDRA PREDESCU 3,4, ȘTEFANIA-IRINA DUMITREL 3,4, CRISTINA DUMITRESCU 3,4, FLAVIA CRIȘAN 3,4, IOAN SMULTEA 5 , DANIELA SAȘCO 6, DAN ILIESCU 7

1 Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
2 Department of Management, Legislation and Communication in Dentistry, Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania 3 Research Centre for Pharmaco-Toxicological Evaluations, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4 Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
5 Doctoral School, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
6 Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
7 Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timișoara, Romania

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Pancreatic ductal adenocarcinoma (PDAC) is a global public health issue and ranks among the top causes of death. Statisti- cally, it is the third leading cause of cancer-related deaths in developed countries, including Europe. Given the current unsat- isfactory treatment options, the concept of drug repurposing (the use of approved drugs for other purposes) represents an alternative approach of interest in pancreatic cancer. For this reason, this research proposes to explore the potential effects of digoxin and digitoxin, two digitalis compounds, on cytotoxicity, pro-apoptosis and antiproliferation in MIA PaCa-2 pancreat- ic cancer cells, in light of the limited and inconclusive results regarding the ability of these drugs in pancreatic cancer thera- py. Towards this purpose, DGX and DGTX were evaluated on the cells using several types of preclinical experiments (MTT assay, bright-field morphological analysis, nuclear assessment through Hoechst 33342, mitochondrial via MitoTracker, acri- dine orange/propidium iodide analysis regarding the occurrence of apoptosis and necrosis and colony formation assay), as well as in ovo assessment of each agent’s irritant capacity on the chorioallantoic membrane using the HET-CAM method.