ArticleMedical oncology (Northwood, London, England)2025
Portimine A maintains bioactivity following exposure to liver microsomes and cell lysates: no evidence for significant metabolic inactivation.
Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposePortimine is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum. This compound has potent apoptotic activity against cancer cells in culture. However, despite the high cytotoxicity of portimine in vitro, it has low toxicity in vivo in comparison to related cyclic imine compounds. It was hypothesised that metabolism of portimine contributed to its reduced toxicity.
methodsCytotoxicity of portimine A was assessed in four murine and one human cancer cell line. In vitro metabolism of portimine was performed in liver S9 fractions and microsomes from human and mouse, with paclitaxel as control, and in the lysates of cultured cells. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to measure the concentrations of portimine in the biological samples.
resultsThe concentration of portimine that reduced cell viability by 50% ranged from 2.0 to 2.6 nM. LC-MS/MS analysis found insignificant losses of portimine in mouse or human liver fractions or cell lysates. There was also no reduction in bioactivity when these biological samples containing portimine were added to cancer cell lines.
conclusionThe data showed that exposure to cellular metabolism did not lead to significant loss of portimine bioactivity. This is valuable information for the development of portimine as a therapeutic agent, but it does not explain the limited in vivo toxicity in comparison to other cyclic imines.
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