Apoptosis cancer

S. B., and Cohen, G.M., The Apaf-1 apoptosome a large caspase-activating complex, Biochemie 84, 203-214, 2002 Shi, Y, Apoptosome the cellnlar engine for the activation of caspase-9. Structure 10, 285-288,2002 Reed, J.C., Apoptosis-based therapies, Afat. Rev. Drag DAc. 1,111-121,2002 Adams, JJVl. and Cory, S., Apoptosomes engines for caspase activation, Curr. Opin. Cell Biol. 14,715-720,2002 Hajra, K.M. and Liu, J.R., Apoptosome dysfunction in human cancer, Apoptosis 9, 691-704, 2004. 

Amentoflavone induced breast cancer apoptosis through blockade of fatty acid synthesis. Sumaflavone and amentoflavone inhibited UV irradiation induced activity of matrix metalloproteinase-1 (MMP-1) in... 

HCypD (hCyp22) Breast, ovarian, uterine cancers Apoptosis repressor 73... 

Meng RD, McDonald ER, Sheikh MS, Fornace AJ, El-Deiry WS. The TRAIL decoy receptor TRUNDD (DcR2, TRAIL-R4) is induced by adenovirus-p53 overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dpendent colon cancer apoptosis. Mol... 

Palozza et al. [20] Prostate cancer Colon cancer Apoptosis and cell growth inhibition by altering mevalonate pathway and Ras signaling Lycopene may alter mevalonate pathway through inhibition of HMG-CoA reductase. This may induce a decreased prenylation of Ras, which, in turn, may modulate redox-sensitive molecular pathways responsible for NF-kB activation and consequently, for cell cycle arrest and apoptosis induction, as evidenced by decreased cyclin D1 and pAKT levels increased p21, p27, and p53 levels and changes in Bax Bcl-2 ratio... 

Biological Applications Detecting cardiolipin, mitochondrial membrane potential, risk of type 2 diabe-21 22 2" tes, cardiotoxicity, prostate cancer apoptosis as-... 

Keywords Nitric oxide S-Nitrosylation Cancer Apoptosis Angiogenesis Metastasis... 

There is a reasonable basis for cancer apoptosis in the electrophilic theory of Miller Miller (1977, 1981), which assumes a positively... 

Besides direct apoptosis effectors, there are a number of other diugs which influence the above explained apoptosis pathways more indirectly. This class of diugs includes molecules which inhibit survival pathways like e.g. the Ras/Raf kinase pathway, the NF-kB pathway and many others. Also inhibitors of survival cytokines which are sometimes produced by cancer cells in an autocrine fashion can render cells susceptible to apoptosis and, hence, effective cancer therapy. These include, but are not limited to, ligands for dependence receptors and cytokines like e.g. interleukin-4. 

Kerr JF, Wyllie AH, Currie G (1972) Apoptosis a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26 239-257... 

ALG-2 is the fust calcium-binding protein of the EF-hand family found to be directly involved in apoptosis. ALG-2 is a 22 kDa protein and like the other members of the penta EF-hand family, contains five EF-hands, with only two of them functional. ALG-2 protein is expressed in the brain and eye and was found to be upregulated in various cancer tissues. Several targets have been found, such as proteins AEP, Alix, preflin, and annexins, suggesting a putative role of ALG-2 in apoptosis. 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

A substantial amount of indirect evidence supports the contention that the induction of apoptosis in tumor cells is critical to successful therapy. Cancer therapy might therefore be viewed as an attempt to induce apoptosis in a population of cells that have undergone selection for apoptotic defects. If correct, this hypothesis would suggest why cancer therapy is in many cases unsuccessful. However, recent studies indicate that this fundamental problem can be circumvented. Progress in the identification of molecules key to the cell death pathways has led to a growing understanding of how apoptosis occurs [3]. It has become clear that pathways to apoptosis are numerous and often interconnected. A solution to the clinical problem of therapeutic resistance, then, may lie in the fact that there appears to be multiple ways that a cell death program can be implemented. 

Alterations to the P53 gene are the most common genetic defects known in cancer [5]. The protein product of P53 is involved in a number of pathways that directly and indirectly lead to apoptosis. Many genes that are involved in apoptosis can be induced by this protein, which is a transcriptional transactivator. The emerging hypothesis is that p53 is a central node of a complex apoptotic network that may function differ ently in diver se cell types and tissues. For example, Bax, the prototype proapoptotic member of the Bcl2 family, can be transcriptionally induced by p53 in certain, but not all, cell types. Like p53, Bax can modulate the extent to which cells are sensitive to apoptosis caused by therapeutic agents. 

Many of the agents currently in use for the therapy of cancer can trigger apoptosis in cancer cells. Cancer-associated alterations of the genes that regulate apoptosis would therefore be predicted to affect sensitivity to these agents. 

Brown JM, Wouters BG (1999) Apoptosis, p53, and tumor cell sensitivity to anticancer agents. Cancer Res 59 1391-1399... 

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

These arotinoids, which were first introduced for the treatment of skin diseases, may also have potential as anticancer diugs. For example, the synthetic retinoid 6-[3-(l-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) has been shown to induce apoptosis in a variety of cancer cells including lung cancer cells in vitro, and studies concerning the use of this agent in vivo would be desirable. 

---