Wednesday, December 26, 2012

Apoptosis. 2006 Feb;11(2):143-9.

Cathepsin-regulated apoptosis.


Institute of Immunology, Otto-von-Guericke-University, Magdeburg, Germany.


Apoptosis can be mediated by different mechanisms. There is growing evidence that different proteolytic enzymes are involved in the regulation of apoptosis. Cathepsins are proteases which, under physiologic conditions, are localized intralysosomally. In response to certain signals they are released from the lysosomes into the cytoplasm where they trigger apoptotic cell death via various pathways, including the activation of caspases or the release of proapoptotic factors from the mitochondria. Here, we review different mechanisms that induce the release of lysosomal enzymes, and the functional relevance of defined cathepsins in defined models of apoptosis.
[PubMed - indexed for MEDLINE] 
Once again we remind our readers that the failure of chemotherapy to lead to a cure has led to the belief that trying to kill the cell indiscriminately has proven somewhat futile.
Giving only less than 20% cure rates.  We needed to be smart by exploiting natural path to death. Indeed the cell has a naturally programmed death called Apoptosis.  Our approach to cure is to find ways to induce cancer cells into Apoptosis.  It is apparent that Apoptosis whenever triggered appears to be better in achieving death of cancer cells.  There are also some non Apoptotic ways to cancer cell death that we discussed in our previous posts.
In Mitochondria, membranous events release Cytochrome C which in turn activates the Caspase family to lead to cell death.  (BAX is linked to Caspase activation)
In the Lysosmes, membranous events seems to free more Cathepsins to lead to Cell death.  We also have shown that Ion Pumps maintain intralysosomal Ph gradiant to allow function of various Hydrolases which function only at Acidic Ph.

Autophagia and Necrosis are some of the other path to cell death.  Our task is to know how to harness these powerful pathways to death.  Response rates are up to 75% in LUNG CANCER using current Oncogene drivers recommendation.

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