Necroptosis: an alternative cell death program defending against cancer

Abstract

One of the hallmarks of cancer is resistance to programmed cell death, which maintains the survival of cells en route to oncogenic transformation and underlies therapeutic resistance. Recent studies demonstrate that programmed cell death is not confined to caspase-dependent apoptosis, but includes necroptosis, a form of necrotic death governed by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as a critical cell-killing mechanism in response to severe stress and blocked apoptosis, and can be induced by inflammatory cytokines or chemotherapeutic drugs. Genetic or epigenetic alterations of necroptosis regulators such as RIP3 and cylindromatosis (CYLD), are frequently found in human tumors. Unlike apoptosis, necroptosis elicits a more robust immune response that may function as a defensive mechanism by eliminating tumor-causing mutations and viruses. Furthermore, several classes of anticancer agents currently under clinical development, such as SMAC and BH3 mimetics, can promote necroptosis in addition to apoptosis. A more complete understanding of the interplay among necroptosis, apoptosis, and other cell death modalities is critical for developing new therapeutic strategies to enhance killing of tumor cells.

Physico-chemical properties based differential toxicity of graphene oxide/reduced graphene oxide in human lung cells mediated through oxidative stress

“…S9). Our results are in accordance to the previous computer simulation study involving artificial membrane which suggested the translocation of large graphene sheets inside membrane via penetration compared to small sheets46. Including this, the presences of negatively charged groups on the surface of GO provide a strong electrostatic interaction between GO sheets and membrane leading to close interaction and provoke a physical damage which could be accounted for their presence in the cell cytoplasm4748.…”

Anticarcinogenic effects of water extract of sporoderm-broken spores of Ganoderma lucidum on colorectal cancer in vitro and in vivo

“…Recently, a growing number of studies indicate necroptosis, distinct from apoptosis and necrosis, as a new mechanism of cell death (63). Cells can readily switch from one form of death to another (64).…”

Release of Cathepsin B in Cytosol Causes Cell Death in Acute Pancreatitis

“…The mechanism for this kind of switch is not known and is an interesting area of investigation for future studies. It is known though that regulated necrosis induced by multiple triggers involves receptor interacting protein kinase-1 (RIP-1) activating receptor interacting kinase-3 (RIP-3) and forming a complex of RIP1/RIP3 called necrosome complex 33 . Activated RIP3 then phosphorylates the downstream substrate that leads to membrane disruption.…”