Silvana Filieria, Giuseppe Micalizzib, Morena Miciacciaa, Danilo Donnarummab, Olga Maria Baldellic, Anselma Liturric, Domenico Armenisec, Luigi Leonardo Palesea, Maria Grazia Perronec, Savina Ferorellic, Luigi Mondellob,d, Paola Dugob,d, Antonio Scilimatic, Anna Maria Sardanellia

aDepartment of Translational Biomedicine Neuroscience "DiBraiN", University of Bari Aldo Moro, Bari, ITALY
bMessina Institute of Technology c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, ITALY
cResearch Laboratory of Woman and Child Health c/o Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Bari, ITALY
dChromaleont s.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, ITALY

Alterations in lipid metabolism is a well-documented phenomenon in cancer. Diffuse intrinsic pontine glioma (DIPG) is a particularly aggressive cancer and leading cause of brain tumor death in children (4-7years). DIPG onsets in the pons, and at diagnosis is diffuse and hence surgically inoperable. In this study, we analyzed the lipidomic pattern in the DIPG-36 cell line and the neuroblastoma cells SHSY-5Y, in absence and presence of ONC201 and THX6, two promising drug-candidates. The lipid profile of SU-DIPG-36 cell line and immortalized neuroblastoma cell line SH-SY5Y was analyzed in the presence and absence of ONC201 and THX6, by using gas chromatography and liquid chromatography analytical techniques coupled to mass spectrometry detection. ONC201 and THX6 induced significant alterations in the cell lipidomic. 

Particularly, in SH-SY5Y cells, an increase in C16:0 and C18:0 after treatment with both compounds, and a simultaneous decrease in the content of C16:1n7 and C18:1n9 was observed. A similar pattern is also found in SU-DIPG-36 cells, although in less extent probably due to higher starting levels of C16:0 in untreated cells. Significant variability in term of intact lipids, especially phosphocholine family was observed upon treatments. The observed lipidomic pattern suggests an inhibition of the stearoyl-CoA desaturase enzyme, that would appear to be less active in SU-DIPG-36, by ONC201 and THX6. These data could also be related to the efficacy of ONC201 and THX6 in suppressing the tumour growth. Interestingly, this enzyme is known to be involved in cancer pathogenesis.

Acknowledgements: (a) NEXTGENERATIONEU (NGEU) funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DD N. 1553 11.10.2022), and project HPC –“National Centre for HPC, Big Data and Quantum Computing – HPC” "Simulazioni, calcolo e analisi dei dati ad alte prestazioni “code CN000000013 (DD N. 3138 16.12.2021); (b) Italian Foundations: Fondazione Progetto GAIA (Marche), Heal Foundation (Lazio), Onlus Mia Neri Foundation (Lazio) and Matibellula Foundation (Piemonte) for their support in the form of studentship.

Keywords: Lipidomic, Diffuse Intrinsic Pontine Glioma, GC and HPLC, Drug development