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
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 29, 2021
- Source ID
- 10.3390/ijms22094699
Entities
People
- Adrianne L Jenner
- Anniina Färkkilä
- Chloé Burlot
- Kate Agopsowicz
- Kyle G. Potts
- Marjut Pihlajoki
- Markku Heikinheimo
- Mary M. Hitt
- Morgan Craig
- Olivia Cardinal
- Powel Crosley
- Yangxin Fu
Organizations
- Research Council of Finland
- United States Department of Defense