Nitric oxide-induced apoptosis in tumor cells
1Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany. V.Umansky@dkfz-heidelberg.de
Advances in Cancer Research
|July 13, 2001
Summary
Nitric oxide (NO) can induce programmed cell death (apoptosis) in tumor cells. This review explores the mechanisms by which NO triggers apoptosis, impacting cancer cell survival.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Nitric oxide (NO) is a crucial signaling molecule involved in neurotransmission, vascular homeostasis, immune regulation, and host defense.
- NO is synthesized from L-arginine by nitric oxide synthase (NOS) enzymes.
- Inducible NOS (iNOS) produces large amounts of NO in macrophages and endothelial cells, exhibiting cytotoxic effects.
Purpose of the Study:
- To review the current knowledge on the role of NO as an effector of apoptosis in tumor cells.
- To discuss the detailed mechanisms underlying NO-mediated apoptosis.
Main Methods:
- This review synthesizes existing research on NO and apoptosis.
- Focuses on molecular and cellular mechanisms of NO-induced cell death in cancer.
Main Results:
- NO-mediated cytotoxicity against tumor cells is linked to apoptosis.
- Mechanisms include p53 accumulation, mitochondrial dysfunction, altered Bcl-2 family expression, caspase activation, and DNA fragmentation.
- NO can also protect cells from other apoptotic stimuli depending on context.
Conclusions:
- Nitric oxide plays a significant role in inducing apoptosis in tumor cells through complex molecular pathways.
- Understanding these mechanisms is crucial for developing novel cancer therapies targeting NO signaling.
Related Concept Videos
02:49Cancer Therapies
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...