Multiple mechanisms of cell death induced by chelidonine in MCF-7 breast cancer cell line

• Chelidonine, the main alkaloid of C. majus, strongly suppresses MCF-7 cell growth.
• It triggers multiple mechanisms of cell death in MCF-7 breast cancer cells.
• Chelidonine induces apoptosis at very low and autophagy at high concentrations.
• Submicromolar concentrations of chelidonine strongly suppresses telomerase.
• Long exposure of MCF-7 to nanomolars of chelidonine accelerates cell senescence.

In a preliminary study screening anti-proliferative natural alkaloids, a very potent benzophenanthridine, chelidonine showed strong cytotoxicity in cancer cells. While several modes of death have been identified, most of anti-cancer attempts have focused on stimulation of cells to undergo apoptosis. Chelidonine seems to trigger multiple mechanisms in MCF-7 breast cancer cells. It induces both apoptosis and autophagy modes of cell death in a dose dependent manner. Alteration of expression levels of bax/bcl2, and dapk1a by increasing concentration of chelidonine approves switching the death mode from apoptosis induced by very low to autophagy by high concentrations of this compound. On the other hand, submicromolar concentrations of chelidonine strongly suppressed telomerase at both enzyme activity and hTERT transcriptional level. Long exposure of the cells to 50 nanomolar concentration of chelidonine considerably accelerated senescence. Altogether, chelidonine may provide a promising chemistry from nature to treat cancer.