Cell death is a crucial process in normal development, tissue homeostasis, and disease. The main form of cell death relevant to cancer is apoptosis, or programmed cell death (PCD), a highly regulated mechanism of cell removal that maintains tissue homeostasis by eliminating unwanted or damaged cells. During apoptosis, cells undergo a series of distinct morphological and biochemical changes, such as DNA fragmentation, membrane blebbing, and caspase activation resulting in a controlled dismantling of cells without releasing potentially harmful intracellular contents into the surrounding tissue. Intrinsic and extrinsic apoptosis are the two distinct pathways that cells can undergo to initiate apoptosis. In intrinsic apoptosis (also known as the mitochondrial pathway) apoptosis is initiated by internal signals, primarily involving the mitochondria, and is triggered by various cellular stresses, such as DNA damage, senescence, or the presence of excessive reactive oxygen species (ROS). Such stress signals then release cytochrome c from the mitochondria into the cytoplasm where it binds the adaptor protein Apaf-1 (apoptotic protease-activating factor 1), ultimately leading to the formation of a multiprotein complex called the apoptosome. Once formed, the apoptosome recruits and activates "initiator" caspases such as caspase-8 and caspase-9, which trigger a cascade of additional activations of "executioner" (effector) caspases such as caspase-3, caspase-6, and caspase-7, that are synthesized as inactive proenzymes and proteolytically cleaved and activated by initiator caspases. Activated executioner caspases then cleave various cellular substrates, including structural proteins, cytoskeletal components, and nuclear proteins, ultimately resulting in the dismantling of the cell. Intrinsic apoptosis is tightly regulated by the balance of both pro-apoptotic and anti-apoptotic proteins, such as members of the Bcl-2 family associated with mitochondria. Perturbations in this balance can lead to abnormal cell survival or excessive cell death. The second form of apoptosis occurs via the extrinsic (or death receptor) pathway. Extrinsic apoptosis is initiated by external signals such as tumour necrosis factor-alpha (TNF alpha). When TNF alpha binds to its receptor (TNF receptor 1 (TNFR1)), it triggers the assembly of a protein complex known as the death-inducing signalling complex (DISC), consisting of TNFR1, adaptor proteins, and initiator caspases. Once the DISC is formed, initiator caspase-8 or caspase-10 are activated, which in turn activate downstream effector caspases, such as caspase-3, caspase-6, and caspase-7. Two other forms of cell death are also important in cancer: necrosis/necroptosis and autophagic cell death. Necrosis is a less controlled form of cell death, usually caused by external factors such as trauma, toxins, or lack of oxygen and characterized by cellular swelling, membrane rupture, and release of intracellular contents, leading to inflammation and tissue damage. In cancer, necrotic cell death often occurs in the core of solid tumours due to hypoxia and nutrient deprivation. In autophagic cell death, the excessive or uncontrolled activation of autophagy leads to the destruction of essential cellular components, ultimately resulting in cellular dysfunction and death. Autophagic cell death is characterized by the presence of increased autophagosome formation, and the absence of typical features associated with apoptosis. Overall, defects in cell death pathways contribute to tumorigenesis by allowing the survival and proliferation of damaged cells, whilst promoting cell death in cancer cells is a fundamental objective of many cancer treatment strategies. Various therapies, such as chemotherapy, radiation therapy, and targeted therapies, aim to induce cell death in cancer cells whilst minimizing damage to healthy tissues. Additionally, targeting specific cell death pathways or manipulating the balance between cell survival and death processes may offer novel approaches for cancer therapy. We offer a comprehensive product catalogue of research tools for studying cell death, including Bcl-2 antibodies, AKT1 antibodies, NF-kB p65 antibodies, NF-kB p65 ELISA Kits, and IGFBP3 ELISA Kits. Explore our full cell death product range below and discover more, for less. Alternatively, you can explore our Apoptosis, Autophagy, and Necroptosis product ranges.