Effect of Precipitated Extracellular Marennine on Angiogenesis and Tumour Cell Proliferation

Angiogenesis is a fundamental biological process involved in the formation of new blood vessels from the pre-existing vascular network. In addition to physiological processes, angiogenesis is also implicated in pathological conditions such as tumour growth and metastatic progression. Research on marennine, a water-soluble blue-green pigment produced by the marine diatom Haslea ostrearia, has highlighted various promising biological activities. In vivo studies have suggested the potential of marennine in cancer treatment. However, these studies were conducted with crude extracts, the exact composition of which remained poorly defined. In this context, our study aimed to explore the effects of marennine on angiogenesis and tumour proliferation by using a Precipitated Extracellular Marennine (PEMn) extract. Our results confirmed the antiproliferative properties of PEMn on several cancer cell lines associated with angiogenic tumours. We then analysed its impact on the key steps of the angiogenic process, including Endothelial Colony-Forming Cells (ECFCs) proliferation, migration, and tubulogenesis. In parallel, we investigated the underlying mechanisms of its action, notably by assessing its effects on cell cycle regulation, senescence, and apoptosis. PEMn significantly inhibited tumour cell proliferation, induced ECFC senescence and apoptosis, impaired migration and tubulogenesis, and downregulated VEGFR-1 expression, highlighting its potential as a novel marine-derived antiangiogenic compound. These findings provide deeper insights into the mechanisms of action of marennine, identifying this bioactive natural compound as a novel bioactive compound in cancer treatment.