The effect of cPLA2 inhibition in basal-like breast cancer

Introduction: Altered metabolism in cells is a hallmark of cancer and cytosolic phospholipase A2 (cPLA2) is a ubiquitous enzyme involved in inflammation. Recent studies has also suggested a possible involvement in various cancer forms, including basal-like breast cancer. The objective of this project was to evaluate the effects of cPLA2 inhibition by the novel drug AVX235 on proliferation and metabolism in basal-like breast cancer in vitro and in vivo with special focus on choline and glucose metabolism.

Methods: Histopathological samples from patient-derived triple-negative BLBC models from previous studies were analyzed with respect to proliferative markers. The cytotoxicity of AVX235 on several breast cancer cell lines was measured. 1H and 13C NMR spectroscopy with MDA-MB-231 cells was performed and resulting metabolite profiles were evaluated by PCA and personal analysis.

Results: IC50 of AVX235 was identified around 27 µM for tested cell lines. 1H NMR analysis of cell extracts gave well resolved spectra. AVX235 treated samples showed highest levels in all metabolites. 13C NMR analysis showed different metabolite profile spectra and mitotic cells counting did not show inhibition of proliferation in breast cancer cells; however, results are not solid due to the limited data.

Conclusion: In these results, we observed that 10 µM concentration AVX235 has no inhibitory effect on proliferation of MDA-MB-231 cells in response to cPLA2 inhibition, which is supported by metabolic activity from 1H NMR spectra results too. Data was limited by few samples or technical errors. Thus, the effect of AVX235 on proliferation and the choline and glucose metabolism needs more research.

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NTNU