Regulated and apoptotic cell death after nanosecond electroporation

Abstract

This chapter will focus on how nanosecond pulsed electric fields (nsPEFs) induce apoptosis and regulated cell death (RCD) in cells in vitro. When studies analyzing nsPEF-induced cell death (CD) began, apoptosis was the only RCD mechanism known and was contrasted with primary "necrosis" or accidental cell death (ACD), when plasma membranes (PMs) immediately lose integrity. Now that necrosis is known to be programmed, the term "necrosis" has become ambiguous. Several RCD mechanisms are now known and nsPEFs induce apoptosis as well as other non-apoptotic RCD mechanisms in a cell-type-dependent manner. This chapter will emphasize apoptotic CD because it is a hallmark of cancer. Cell fate is determined by a balance between anti-apoptotic survival mechanisms and pro-apoptotic CD mechanisms. These schemes will be outlined. Extrinsic and intrinsic apoptosis mechanisms will be defined and a review of methods to determine apoptosis, including their caveats and limitations, will be discussed. Examples will be given of some cellular "sensors" and how nsPEFs might activate them. Molecular mechanisms that induce apoptosis and other RCD mechanisms will be presented. Overall, what is presently known about nsPEFinduced apoptosis and RCD will be covered.