The emerging role of paraptosis in tumor cell biology: Perspectives for cancer prevention and therapy with natural compounds

Standard anti-cancer therapies promote tumor growth suppression mainly via induction of apoptosis. However, in most cases cancer cells acquire the ability to escape apoptotic cell death, thus becoming resistant to current treatments. In this setting, the interest in alternative cell death modes has recently increased. Paraptosis is a new form of programmed cell death displaying endoplasmic reticulum (ER) and/or mitochondria dilation, generally due to proteostasis disruption or redox and ion homeostasis alteration. Recent studies have highlighted that several natural compounds can trigger paraptosis in different tumor cell lines. Here, we review the molecular mechanisms underlying paraptotic cell death, as well as the natural products inducing this kind of cell death program. A better understanding of paraptosis should facilitate the development of new therapeutic strategies for cancer prevention and treatment.