ArticleMolecular cancer therapeutics2015
The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- Novel anti-ITGA4 monoclonal antibody induces cell death via large pore formation in NK/T-cell lymphoma cells.Scientific reports · 2025Article
- A Phase 0 Window of Opportunity Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Patients with Recurrent Gliomas.medRxiv : the preprint server for health sciences · 2025Article
- LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models.Pharmaceutics · 2025Article
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.Cancer discovery · 2024Article
- Review
- Altering phosphorylation in cancer through PP2A modifiers.Cancer cell international · 2024Review
- A Small Molecule Inhibitor of Leucine Carboxyl Methyltransferase-1 Inhibits Cancer Cell Survival.Frontiers in drug discovery · 2024Article
- Loss of EPS8 sensitizes non-small-cell lung carcinoma to chemotherapy-induced DNA damage.Cancer gene therapy · 2023Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Review
- Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer.Molecular cancer therapeutics · 2021Article
- Article
- Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids.PLoS pathogens · 2020Article
- Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma.Journal of neuro-oncology · 2020Article
- Targeting PP2A inhibits the growth of triple-negative breast cancer cells.Cell cycle (Georgetown, Tex.) · 2020Article
- The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.Molecular cancer therapeutics · 2019Article
- CHTOP in Chemoresistant Epithelial Ovarian Cancer: A Novel and Potential Therapeutic Target.Frontiers in oncology · 2019Article
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3, OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling. In vivo studies were conducted in an intraperitoneal metastatic mouse model using SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and γH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly enhanced tumor growth inhibition and prevented disease progression after treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.
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