Apoptotic systems

The rationale of cancer chemotherapy is based on ceU growth, differentiation, and apoptotic mechanisms of the cell. Carcinogenesis is actuaUy a multistep process that occurs within years. This is because the human cell has many defense mechanisms for protecting DNA. The number of ceUs in an individual is controlled by ceU division and apoptotic systems. DNA mutations that affect the genes that control either cell cycle (cell division) or apoptosis result in an excessive number of mutated cells and that is cancer. Nowadays, there are a few cancer cell population kinetics hypotheses (i.e., Norton-Simon, Gompertzian model) and... 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that... 

Although cadmium is not strongly mutagenic, it is known that it causes increased oxidative DNA damage and that it inhibits the DNA repair systems. It has also been found to induce cell death both by necrosis and apoptosis. Since the latter is extremely calcium-dependent, it seems likely that the pro-apoptotic effects of cadmium are due to its interference with calcium homeostasis. 

Tseng SC, Kruse FE, Merritt J, Li DQ. Comparison between serum-free and fibroblast-cocultured single-cell clonal culture systems Evidence showing that epithelial anti-apoptotic activity is present in 3T3 fibroblast-conditioned media. Curr Eye Res 15 973-984 (1996). 

Pradhan, D., Krahling, S., Williamson,. P, and Schlegel, R.A., 1997, Multiple systems for recognition of apoptotic lymphocytes by macrophages. Mol. Biol. Cell. 8 767-778. 

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