Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action.

摘要: Portoamides are cyclic peptides produced and released by the cyanobacterial strain Phormidium sp. presumably to interfere with other organisms in their ecosystems ("allelopathy"). were previously demonstrated have an antiproliferative effect on human lung carcinoma cells, but underlying mechanism of this activity has not been described. In present work, effects portoamides proliferation examined eight cancer cell lines two non-carcinogenic lines, major differences sensitivities observed. To generate hypotheses regard molecular mechanisms action, quantitative proteomics using 2D gel electrophoresis MALDI-TOF/TOF performed colon line HT-29. The expression proteins involved energy metabolism (mitochondrial respiratory chain pentose phosphate pathway) was found be affected. hypothesis altered tested further experiments. Exposure resulted reduced cellular ATP content, likely due decreased mitochondrial production. Mitochondrial hyperpolarization reductive capacity observed treated cells. Furthermore, alterations peroxiredoxins (PRDX4, PRDX6) components proteasome subunits (PSB4, PSA6) portoamide-treated these associated detectable increases oxidative stress. We conclude that cytotoxic is disturbance metabolism, structure function.