Abstract A025: Cytostatic effects and expression modulations in cell cycle genes by a 3rd generation alkyl-phospholipid (erufosine) in liver and lung cancer cells

Abstract

Abstract Introduction: Alkyl-phospholipids (ALPs) are a family of compounds that have affinity to cell membranes and have demonstrated antineoplastic potential. Erufosine is a 3rd generation ALP that can be injected intravenously for its long (22-carbon) chain with a cis-13,14 double bond. Erufosine, like other ALPs, causes changes in the lipid rafts of the cell membrane and exerts its anticancer effects through cytotoxic and cytostatic mechanisms. In this study, intentions were to investigate erufosine mediated cytostatic effects in liver and lung cancer cells at functional and molecular levels. Materials and Methods: Liver (HepG2) and lung (H1299) cancer cell lines were exposed to various concentrations of erufosine (1.56-50µM) and resulting anti-proliferative effects were monitored via MTT dye reduction assay. Cytostatic effects of erufosine on the two cancer cell lines were investigated via propidium iodide-based DNA staining and FACS analysis. A real time PCR based panel was used to decipher the impact of erufosine exposure on 84 cell cycle related genes in the two cancer cell lines. Fold changes were identified via the Livak method while untreated cells were used as controls. Results: Erufosine induced the anti-proliferative effects in both cancer cell lines, however, lung cancer cells were more sensitive (IC50: 6.25µM) as compared to liver cancer cells (IC50: 33µM). The compound induced a comparable cell cycle arrest in S phase in the cancer cell lines as reflected by more accumulation of the cells in this particular phase. Exposure with erufosine (IC50/48 hours) de-regulated the cell cycle related genes in both cancer cell lines. Again, the lung cancer cells were more responsive in comparison to liver cancer cells as reflected by a substantial de-regulation (≥2fold) of 35/84 (42%) and 13/84 (15%) genes, respectively. Conclusion: The findings of this study confirmed erufosine mediated anti-proliferative and cytostatic effects in the liver and lung cancer cells. Furthermore, the compound induced substantial alterations in cell cycle related genes in the two cancer cell lines. Present findings foster further research to investigate the antineoplastic effects induced by erufosine in liver and lung cancer cells to support its clinical utilization. Citation Format: Asim Pervaiz, Marriyam Nasim, Nazakat Shafiq, Martin R. Berger. Cytostatic effects and expression modulations in cell cycle genes by a 3rd generation alkyl-phospholipid (erufosine) in liver and lung cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A025.