Induction of apoptosis in breast cancer cells by naphthylisoquinoline alkaloids

Breast cancer is one of the most common types of cancer in the world and a major cause of mortality. Present therapeutic strategies against breast cancer have severe drawbacks such as allergies, damage to healthy tissues, reoccurrence of cancer, and emergence of drug resistance. Naphthylisoquinoline alkaloids are a group of structurally unique natural products produced by tropical lianas belonging to the plant families Dioncophyllaceae and Ancistrocladaceae indigenous to Asia and Africa. These secondary metabolites have been reported to show anti-infective activity, but they also act against leukemic and pancreatic cancer cells. In the present study we have tested the potential of eleven mono- and dimeric naphthylisoquinoline compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Three out of the compounds (agents 1, 4, and 11) showed significant activities against both tested cancer cell lines. Further mechanistic investigations revealed that all of the three substances induce apoptotic cell death via its intrinsic pathway by causing deformation of the nuclear membrane, disruption of the mitochondrial membrane potential (MMP), and elevated reactive oxygen species (ROS) production in both cell lines. Flow cytometric analysis using Annexin V - FITC/PI double staining showed an increased number of apoptotic cells in both, the early and the late phases.