RRC ID 72460
Author Crosley P, Farkkila A, Jenner AL, Burlot C, Cardinal O, Potts KG, Agopsowicz K, Pihlajoki M, Heikinheimo M, Craig M, Fu Y, Hitt MM.
Title Procaspase-Activating Compound-1 Synergizes with TRAIL to Induce Apoptosis in Established Granulosa Cell Tumor Cell Line (KGN) and Explanted Patient Granulosa Cell Tumor Cells In Vitro.
Journal Int J Mol Sci
Abstract Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apoptosis-inducing agents. Sensitivity of the AGCT cell line KGN to these drugs, alone or in combination with PAC-1, was tested using a viability assay. Our results show a wide range in cytotoxic activity among the agents tested. Synergy with PAC-1 was most pronounced, both empirically and by mathematical modelling, when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This combination showed rapid kinetics of apoptosis induction as determined by caspase-3 activity, and strongly synergistic killing of both KGN as well as patient samples of primary and recurrent AGCT. We have demonstrated that the novel combination of two pro-apoptotic agents, TRAIL and PAC-1, significantly amplified the induction of apoptosis in AGCT cells, warranting further investigation of this combination as a potential therapy for AGCT.
Volume 22(9)
Published 2021-4-29
DOI 10.3390/ijms22094699
PII ijms22094699
PMID 33946730
PMC PMC8124867
MeSH Antineoplastic Combined Chemotherapy Protocols Apoptosis / drug effects Benzoquinones / administration & dosage Carboplatin / administration & dosage Caspase 3 / metabolism Cell Line, Tumor Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives Dose-Response Relationship, Drug Drug Synergism Enzyme Activation / drug effects Female Gemcitabine Granulosa Cell Tumor / drug therapy* Granulosa Cell Tumor / enzymology Granulosa Cell Tumor / pathology Humans Hydrazones / administration & dosage* In Vitro Techniques Mathematical Concepts Models, Biological Ovarian Neoplasms / drug therapy* Ovarian Neoplasms / enzymology Ovarian Neoplasms / pathology Piperazines / administration & dosage* TNF-Related Apoptosis-Inducing Ligand / administration & dosage*
IF 4.556
Human and Animal Cells KGN(RCB1154)