Abstract 116: Erufosine, a third-generation alkylphosphocholine with cytotoxic and cytostatic effects in breast and colorectal cancer cells
Authors: Pervaiz Asim , Mahmood Saqib , Berger Martin R. 
Published: July 2017

Introduction Breast and colorectal cancers are highly malignant diseases with low 5-year survival rate (&lt;21%) in advanced stages, which highlights the need of finding new therapeutic options. Considering this, we are interested in exploring the anticancer potential of erufosine, a membrane targeting synthetic lipid analogue belonging to a class of antineoplastic agents known as alkylphosphocholines (APCs). Properties such as intravenous administration and significantly reduced hemolytic activity as compared to previous APC generations, and efficient cytotoxic effects against malignant cells make it an attractive anticancer compound.

Materials and Methods In the present experiments, we studied the effects of erufosine against breast (MDA-MB-231 and MCF-7) and colorectal (SW480 and SW620) cancer cell lines. Following exposure to erufosine (0.78-100µM) for 24, 48 and 72h, cytotoxic effects were measured by MTT dye reduction assay and inhibitory concentrations (IC) were identified by GraphPad Prism software 6. Erufosine mediated cytostatic effects were highlighted by means of propidium iodide (PI) based labeling of the DNA followed by flow cytometry analysis. Furthermore, the cells were exposed to increasing concentrations of erufosine (IC25, 50, 75) and alterations in cell cycle relevant genes (CCNA1, CCND1, CCNE1, CCNE2, CDK1, CDK4) were investigated by qRT-PCR methodology.

Results Erufosine was highly active against the selected cell lines (IC50 &lt; 10µM, 24h) and induced significant arrest in the G2/M phase of the cell cycle. The cytostatic effects were more pronounced in the two metastatic cell lines of breast (MDA-MB-231) and colorectal (SW620) cancers. At molecular levels, erufosine induced expression of CCNA1 (≥ 2fold) in SW480, SW620, and MCF-7 cells, while the expression was inhibited in MDA-MB-231 cells at high concentrations (IC50, IC75). There were no significant alterations (≤ 2fold) in the expression levels of CCND1, CCNE1 and CDK4 in the four cell lines. CCNE2 was significantly downregulated in breast cancer cell lines only. Noteworthy, alterations in CDK1 were associated with cell lines from primary cancers, where the expression was upregulated in SW480 cells and downregulated in MCF-7 cells.

Conclusion Antineoplastic effects of erufosine contribute to decreased proliferation of breast and colorectal cancer cell lines. This synthetic lipid induces arrest in G2/M phase and alterations in cell cycle relevant genes in the selected panel of breast and colorectal cancer cells. Characteristics like in vivo stability, minimal hemolytic activity, no toxicity to bone marrow and antineoplastic effects (cytotoxic/cytostatic) against cancer cells make it an attractive therapeutic compound. Further understanding at molecular levels supported by in vivo experimentation will pave the way to validate its therapeutic potential against cancers.

Citation Format: Asim Pervaiz, Saqib Mahmood, Martin R. Berger. Erufosine, a third-generation alkylphosphocholine with cytotoxic and cytostatic effects in breast and colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 116. doi:10.1158/1538-7445.AM2017-116