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Prorocentrolide and its analogs, the novel naturally derived antitumor agents, have recently been identified in the dinoflagellate Prorocentrum lima . In the current study, the underlying inhibitory mechanisms of 4-hydroxyprorocentrolide ( 1 ) and prorocentrolide C ( 2 ) on the proliferation of human carcinoma cells were determined. 1 and 2 arrested the cell cycle at the S phase in A549 cells and G2/M phase in HT-29 cells, leading to apoptotic cell death, as determined using fluorescence-activated cell sorting analysis with Annexin V/PI double staining. Apoptosis induced by these compounds was associated with alterations in the expression of cell cycle-regulating proteins (cyclin D1, cyclin E1, CDK2, and CDK4), as well as alterations in the levels of apoptosis-related proteins (PPAR, Bcl-2, Bcl-xl, and survivin). These findings provide new insights into the antitumor mechanisms of 4-hydroxyprorocentrolide and prorocentrolide C and a basis for future investigations assessing prorocentrolide analogs as prospective therapeutic drugs.

toxins

Cytotoxic 4-Hydroxyprorocentrolide and Prorocentrolide C from Cultured Dinoflagellate Prorocentrum lima Induce Human Cancer Cell Death through Apoptosis and Cell Cycle Arrest