Abstract 5408: Chloroquine inhibits PARP expression in hepatoblastoma

Abstract

Abstract Hepatoblastoma is the most common pediatric liver malignancy accounting 1 % of all pediatric malignancies. Despite advances in medical treatment and surgical techniques, the prognosis for advanced metastatic hepatoblastoma remains poor, underscoring the need for new therapeutic modalities. Chloroquine (CQ), a drug used to treat malaria and rheumatologic diseases, has been shown to inhibit the growth and survival of various cancer types. In this study we examined the antineoplastic activity of CQ on HB cells. Established human HB cell line (HUH6) cells were cultured in presence of clinically acceptable concentrations of CQ. Morphology, viability, and apoptosis were assessed after 48 h and 96 h of CQ treatment showing decreased cell survival and increased caspase 3/7 activity representing induction of apoptosis. Metabolomic profiling of CQ treated HUH6 cells demonstrated significant decrease in NAD+ and aspartate concentration. Furthermore, RT-qPCR based Death Pathway Finder array was conducted to elucidate the molecular mechanisms underlying the CQ effect showing downregulated expression of PARP1 and PARP2. Quantitative western blotting was performed to validate differentially expressed genes at the protein level. Taken together, CQ treatment inhibits cell survival in HB cells in vitro, presumably by disturbing NAD+/NADH balance, impairing aspartate biosynthesis, and reducing PARP expression. CQ thus holds potential as a new treatment modality in HB management. Citation Format: Marjut Pihlajoki, Katja Eloranta, Antti Kyrönlahti, Markku Heikinheimo. Chloroquine inhibits PARP expression in hepatoblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5408.