Inhibition of Pancreatic Cancer Cells by Different Amyloid Proteins Reveals an Inverse Relationship between Neurodegenerative Diseases and Cancer

Abstract

Neurodegenerative diseases and cancers are considered to be two families of diseases caused by completely opposite cell-death mechanisms: the former caused by premature cell death, with the latter due to the increased resistance to cell death. Growing epidemiologic evidence appear to suggest an inverse correlation between neurodegenerative diseases and cancers. However, pathological links, particularly from a protein-cell interaction perspective, between these two families of diseases remains to be proven. Here, a fundamental study investigates the effects of three amyloid proteins of Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC) on pancreatic cancer (PANC-1) cells. Collective results demonstrate a general inhibitory activity of all of three amyloid proteins on cancer cell proliferation, but inhibition efficiencies are strongly dependent on amyloid sequence (Aβ, hIAPP, hCT), concentration (IC25, IC50, IC75), and aggregation states (monomers, oligomers). Amyloid proteins exhibit two pathways against cancer cells: amyloid monomer-induced ROS production to inhibit cell growth and amyloid oligomer-induced membrane disruption to kill cells. Collectively, the results demonstrate a general inhibition function of amyloid proteins to induce cancer cell death by preventing cell proliferation, suppressing cell migration, promoting reactive oxygen species production, and disrupting cell membranes.