TY - JOUR
T1 - Heat Shock Protein 90 Inhibitor Effects on Pancreatic Cancer Cell Cultures
AU - Gulla, Aiste
AU - Kazlauskas, Egidijus
AU - Liang, Hong
AU - Strupas, Kestutis
AU - Petrauskas, Vytautas
AU - Matulis, Daumantas
AU - Eshleman, James R.
N1 - Funding Information:
This work was supported in part by the Sol Goldman Pancreatic Cancer Research Center, the Stringer Foundation, Michael Rolfe Pancreatic Cancer Foundation, Mary Lou Wootton Pancreatic Cancer Research Fund, the Gerald O. Mann Charitable Foundation (Harriet and Allan Wulfstat Trustees), and the Joseph C. Monastra Foundation. We thank Drs Liz Jaffee and Chris Iacobuzio-Donahue for kindly providing the Panc10.05 and A6L cell lines.
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Objectives Pancreatic ductal adenocarcinoma is one of the deadliest cancers for which few curative therapies are available to date. Heat shock protein 90 (Hsp90) inhibitors have shown activity against numerous cancers in vitro; therefore, we tested whether they could be used to target pancreatic ductal adenocarcinoma. Methods Inhibitors of Hsp90 ATPase activity were applied on low-passage pancreatic cell line cultures (Panc10.05, Panc215, A6L) in a dose-response manner, and the inhibitor in vitro effect on cell growth was evaluated. Seven of novel Hsp90 inhibitors based on resorcinol fragment and 5 commercially available Hsp90 inhibitors (17-AAG, AT-13387, AUY-922, ganetespib, and rifabutin) as well as control compound triptolide were tested yielding IC50 values in 2- and 3-dimensional assays. Results The novel Hsp90 inhibitors exhibited strong effects on all 3 tested pancreatic cell line cultures (Panc10.05, Panc215, A6L) reaching the IC50 of 300 to 600 nM in 2- and 3-dimensional assays. Conclusions Novel Hsp90 inhibitors can be developed as antipancreatic cancer agents. Their chemical structures are simpler, and they are likely to exhibit lower side effects than the much more complex inhibitors used as controls.
AB - Objectives Pancreatic ductal adenocarcinoma is one of the deadliest cancers for which few curative therapies are available to date. Heat shock protein 90 (Hsp90) inhibitors have shown activity against numerous cancers in vitro; therefore, we tested whether they could be used to target pancreatic ductal adenocarcinoma. Methods Inhibitors of Hsp90 ATPase activity were applied on low-passage pancreatic cell line cultures (Panc10.05, Panc215, A6L) in a dose-response manner, and the inhibitor in vitro effect on cell growth was evaluated. Seven of novel Hsp90 inhibitors based on resorcinol fragment and 5 commercially available Hsp90 inhibitors (17-AAG, AT-13387, AUY-922, ganetespib, and rifabutin) as well as control compound triptolide were tested yielding IC50 values in 2- and 3-dimensional assays. Results The novel Hsp90 inhibitors exhibited strong effects on all 3 tested pancreatic cell line cultures (Panc10.05, Panc215, A6L) reaching the IC50 of 300 to 600 nM in 2- and 3-dimensional assays. Conclusions Novel Hsp90 inhibitors can be developed as antipancreatic cancer agents. Their chemical structures are simpler, and they are likely to exhibit lower side effects than the much more complex inhibitors used as controls.
KW - 3D cell cultures
KW - Abbreviations
KW - Hsp90 inhibitors
KW - pancreatic ductal adenocarcinoma
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U2 - 10.1097/MPA.0000000000001807
DO - 10.1097/MPA.0000000000001807
M3 - Article
C2 - 33939678
AN - SCOPUS:85105246253
SN - 0885-3177
VL - 50
SP - 625
EP - 632
JO - Pancreas
JF - Pancreas
IS - 4
ER -