Chapter 5 - Bioactive Dietary Compounds Regulate Mitochondrial Apoptosis Signaling in Ambivalent Way to Function as Neuroprotective or Antitumor Agents

Abstract

Abstract Bioactive dietary compounds are proposed as neuroprotective agents to prevent cell death of brain neurons in aging and neurodegenerative disorders, and also as antitumor compounds. Various lines of naturally occurring compounds, such as polyphenols, protect neuronal cells against cell death in animal and cellular models. In the brain, apoptosis is a common mode of neuronal death, and the well-conserved death cascade is activated by oxidative stress, decline in neurotrophic factors, mitochondrial dysfunction, neurotoxins, and excitotoxicity. The mitochondrial death machinery is the most promising target for neuroprotection, and bioactive compounds in food and beverage have been considered to regulate the signal activation by their antioxidant and antiinflammatory functions. Recently we found the regulation of mitochondrial membrane permeability by phytochemicals in apoptosis induced by PK11195, a ligand of the outer membrane translocator in human catecholaminergic SH-SY5Y cells. PK11195 induced transitional permeabilization of the inner mitochondrial membrane and then persistent formation of the mitochondrial permeability transition pore. Bioactive dietary compounds suppressed the initial formation of pore and the following activation of apoptosis cascade. Among natural phytochemicals, ferulic acid analogues and sesame lignans inhibited or activated the mitochondrial permeabilization dependently on their structure. This new function of phytochemicals may determine the fate of cells, independent of their antioxidant, antiinflammatory, and metal chelating function. Controversial regulation of the mitochondrial death signaling by bioactive compound is discussed to develop new series of antiaging and neuroprotective, and antitumor in the future.