Cell Suicide in Health and Disease

By

Meaghan Bence&

Leila Kessler

What is Apoptosis?

An organism’s housekeeping mechanism, maintains health and homeostasis by ridding itself of aging, infected or mutated cells.

This process occurs as a result of a series of cascading cell signals.

Self-destruction of cells is orderly and neat

Apoptosis in Cancer

In neurodegenerative diseases, like Parkinson's, apoptosis is inappropriately activated, killing cells in the brain that are necessary for normal function.

In most cancers, apoptosis of old or mutant cells becomes mistakenly deactivated, and cancer cells reproduce with abandon

Cancer treatments such as chemotherapy and radiation, can affect the life of healthy cells, but it causes apoptosis of abnormal cells.

Apoptosis

Source: Graduate Program in Structural and Cell Biology:Apoptosis. <http://www.wadsworth.org/BMS/SCBlinks/apop.html>(4/4/00)

Apoptosis in Cancer

Breast cancer cells undergoing apoptosis, treated with 50 uMof VP-16 for 0 days(right), 7 days (middle), and 7 days (right).

Source: Graduate Program in Structural and Cell Biology:Apoptosis. <http://www.wadsworth.org/BMS/SCBlinks/apop.html>(4/4/00)

BCL-2 and p53 in Ovarian Cancer Ovarian cancer clinical trials are designed to kill tumor

cells deficient in the p53 gene Several different approaches have shown positive

results with an adenovirus against p53 on other cancers A drug which targets the BCL2 gene has demonstrated

activity in non-Hodgkin's lymphoma clinical trials Combinations of anti-p53 gene therapy with

chemotherapy may improve survival A large number of animal studies show the potential of

an adenovirus targeted against p53 in ovarian cancer

BCL-2 and p53 in Ovarian Cancer

p53 has little predictive value for patient prognosis in late stage disease, poor tumor differentiation, and when residual tumor is present

p53 does not generally predict sensitivity to carboplatin or taxol chemotherapy but some

Experimental results differ, particularly with cisplatin

Aberrations of the p53 gene occur frequently in ovarian cancer

FAS in Cancer“Fas-mediated apoptosis is blocked in tumors with mutations in Fas or in the tumor suppressor gene p53, in enzymes involved in the early caspase cascade, or in tumors expressing abnormal levels of proteins involved in signal transduction. For example, increased resistance towards Fas-mediated apoptosis results from down-regulation of caspase-1 and selective members of the apoptosis-inducing Bcl-2 family of molecules, or by upregulation of Bcl-2. In addition, some tumor cells can prevent Fas Ligand (FasL)-induced apoptosis by the release of soluble Fas (3). Tumors may use FasL/Fas to eliminate Fas-expressing leukocytes, including cytotoxic T-cells (Tc). This may occur through constitutive expression of FasL, or by release of soluble FasL.”

Source:http://inet.uni-c.dk/~iirrh/IIR/07kill/apFasKill.htm (4/4/00)

FAS in Cancer

Source:http://inet.uni-c.dk/~iirrh/IIR/07kill/apFasKill.htm (4/4/00)

ICE-like protiens

Ifsfamide-IFM, carboplatin-CBDCA, etoposide-VP16

It is a well-known treatment of solid tumors, mainly germ-cell tumors (GCTs) and breast cancer

Plays important role in apoptosis ICE homologs are known as caspases and are

found in mammals and nematodes as well as flies