Apoptosis and apoptotic body: disease message and therapeutic target potentials

Abstract

Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches, accumulating a wealth of knowledge which led to not only a better understanding of the fundamental process, but also potent therapies of diseases. The classic intrinsic and extrinsic signaling pathways of apoptosis, along with regulatory factors have been well delineated. Drugs and therapeutic measures designed based on current understanding of apoptosis have long been employed. Small-molecule apoptosis inducers have been clinically used for eliminating morbid cells and therefore treating diseases, such as cancer. Biologics with improved apoptotic efficacy and selectivity, such as recombinant proteins and antibodies, are being extensively researched and some have been approved by the FDA. Apoptosis also produces membrane-bound vesicles derived from disassembly of apoptotic cells, now known as apoptotic bodies (ApoBDs). These little sealed sacs containing information as well as substances from dying cells were previously regarded as garbage bags until they were discovered to be capable of delivering useful materials to healthy recipient cells (e.g., autoantigens). In this review, current understandings and knowledge of apoptosis were summarized and discussed with a focus on apoptosis-related therapeutic applications and ApoBDs.

Tumor microenvironment complexity and therapeutic implications at a glance

“…Apoptosis produces many apoptotic bodies containing a broad spectrum of cell components including DNAs, mRNAs, miRNAs, proteins, and lipids. Following the engulfment of apoptotic bodies by different cell types (macrophages, epithelial cells, fibroblasts, dendritic cells, and endothelial cells) subsequent internalization, devouring, and destruction of corpses occur in the lysosomes [221]. Since apoptotic cell engulfment could cause the generation of molecular memory by macrophages, apoptotic bodies are thought to accelerate intercellular communication via transferring cellular factors [222].…”

Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication

“…Chromatin margination is first limited to thin electron-dense areas underlying the nuclear envelope. These electron-dens areas are then organized in cap-shaped compact structures [25]. During this phase, an unusual translocation of nuclear pores (np), closed to diffuse chromatin zones, appears, but no pore can be observed around the zone of presence of compact areas.…”

“…Moreover, in ApoBDs of larger size, proteins, lipids, RNA, and DNA molecules have been demonstrated [53][54][55]. Presumably, ApoBDs can have important effects on their downstream cells or recipient cells, given their larger molecular pool [25]. Nevertheless, little is known of their function, whereas major scientific progress on the role of EVs in cancer biology has been achieved by investigating exosomes and/or microvesicles [9].…”

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…The distinctive biogenetic process accounts for the fact that MVs can be readily sub-classified based on annexin V positivity, restricted to MVs that expose phosphatidylserine, and patterns of surface markers, which generally reflect those of the parental cells [27,33,47]. However, phosphatidylserine is also exposed on apoptotic bodies, which are larger vesicles specifically formed during the late stages of apoptosis [97,98]. Apoptotic bodies can be distinguished from other phosphatidylserine-positive MVs based on positivity for caspases 3 and 7 and their substrates (e.g., ROCK1 and PANX1) [99], while size is unreliable, because apoptotic bodies (~0.1 to~5 µm) overlap in size with other EV subtypes [99].…”