TY - JOUR
T1 - New Pharmacological Strategies against Pancreatic Adenocarcinoma
T2 - The Multifunctional Thiosemicarbazone FA4
AU - Anobile, Dario P.
AU - Niso, Mauro
AU - Puerta, Adrian
AU - Fraga Rodrigues, Stephanie M.
AU - Abatematteo, Francesca S.
AU - Avan, Amir
AU - Abate, Carmen
AU - Riganti, Chiara
AU - Giovannetti, Elisa
N1 - Funding Information: Funding: This work was partially supported by the following grants: CCA Foundation 2018 grants (to E.G.), KWF Dutch Cancer Society grants (KWF project#19571) (to E.G.); AIRC IG grant 24444 (to E.G.) and IG grant 21408 (to C.R.); CRT Foundation 2021 (#2021-0556 to C.R.); EU Social Fund (FSE) and the Canary Islands ACIISI predoctoral grant TESIS2020010055 and EST2021010019 (to A.P). D.P.A. was supported by the COST Action CA17104 STRATAGEM, supported by COST (European Cooperation in Science and Technology) (www.cost.eu). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 µM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.
AB - A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 µM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.
KW - Chemoresistance
KW - Migration
KW - Multifunctional thiosemicarbazone
KW - Pancreatic cancer primary cultures
KW - σ-2 receptor ligands
UR - http://www.scopus.com/inward/record.url?scp=85126018846&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/molecules27051682
DO - https://doi.org/10.3390/molecules27051682
M3 - Article
C2 - 35268783
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 5
M1 - 1682
ER -