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Tuesday, May 20, 2014

Multicellularity, programmed cell death (apoptosis) and cancer

Way back in time

It was the  journey of one cell..
picture courtesy: http://www.visualphotos.com
One cell behaved as full and free organism in deep sea water
and moved on to a journey of evolution..

Multicellularity was the destined goal

And

Humans were the last one in this series to evolve
and roam on the land..

Much have changed ever since..
picture thankfully shared from:
http://www.bbc.co.uk/nature/
history_of_the_earth
But..

We still have memories in each individual cell stored and intact, 

like..

1. Our cells still do all life-activities in water..
2. Our multicellular journey in embryonic stage still starts with one cell, 
bearing all features of their predecessor species at one or other stage..
(i.e. ontogeny repeats phylogeny)
3. And before coming to land, we still swim in sea-like water of amniotic fluid in mother's womb..

But..

Multicellularity has come up with unique features
for combined survival of trillions
of cell-fellows
for a common-cause,

like..

1. Multicellularity is the ultimate in cooperation,
multiple cells make up an individual
that cooperates for the benefit of the whole. 
 Sometimes cells give up their ability to reproduce for the benefit of close kin..
2. Cells present in multicellular organisms possess the unique property of self-destruction.
They have the genetic information to commit suicide !
This phenomenon is termed as programmed cell death (PCD).
That way stressed and damaged cells kill them self for the benefit of whole..

And.. 

If a single cell negates this self sacrifice....

then it causes cancer, 

And..

The whole lot of cells in an individual body are doom to die

And 

Individuals have to perish !!


Apoptosis: The cells of a multicellular organism are members of a highly organized community. The number of cells in this community is tightly regulated—not simply by controlling the rate of cell division, but also by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an intracellular death program.
The balance between the formation 
of new cells and deletion of the old 
and abnormal cells is vital for all 
physiological processes of the body.

Credit: NIH
This process is therefore called programmed cell death, although it is more commonly called apoptosis (from a Greek word meaning “falling off,” as leaves from a tree).
The most mind-boggling 
phenomenon in cells is the 
mechanism through which they 
determine their own age, and 
when old enough and susceptible 
to damage, they commit suicide. 
Every single day, millions of cells 
die and are replaced by new cells
―a process called cell turnover.
courtesy share:http://www.buzzle.com/
articles/why-do-cells-commit-suicide.html
Necrosis and Apoptosis: Cells that die as a result of acute injury typically swell and burst. They spill their contents all over their neighbors—a process called cell necrosis—causing a potentially damaging inflammatory response. By contrast, a cell that undergoes apoptosis dies neatly, without damaging its neighbors. The cell shrinks and condenses. The cytoskeleton collapses, the nuclear envelope disassembles, and the nuclear DNA breaks up into fragments. Most importantly, the cell surface is altered, displaying properties that cause the dying cell to be rapidly phagocytosed, either by a neighboring cell or by a macrophage (a specialized phagocytic cell), before any leakage of its contents occurs. This not only avoids the damaging consequences of cell necrosis but also allows the organic components of the dead cell to be recycled by the cell that ingests it.

Intracellular regulators of the cell death program: All nucleated animal cells contain the seeds of their own destruction, in the form of various inactive procaspases that lie waiting for a signal to destroy the cell. It is therefore not surprising that caspase activity is tightly regulated inside the cell to ensure that the death program is held in check until needed.

Mitochondrial role in apoptosis: When cells are damaged or stressed, they can also kill themselves by triggering procaspase aggregation and activation from within the cell. In the best understood pathway, mitochondria are induced to release the electron carrier protein cytochrome c  into the cytosol, where it binds and activates an adaptor protein called Apaf-1. This mitochondrial pathway of procaspase activation is recruited in most forms of apoptosis to initiate or to accelerate and amplify the caspase cascade. DNA damage, for example, can trigger apoptosis. This response usually requires p53, which can activate the transcription of genes that encode proteins that promote the release of cytochrome c from mitochondria. These proteins belong to the Bcl-2 family.
(http://www.ncbi.nlm.nih.gov/books/NBK26873/)

Cell suicide related disorder: One of the most disastrous consequences of failure in cell suicide is the dreadful set of diseases called cancer. Other conditions or disorders include congenital defects, like syndactyly (fused fingers), neural tube malformation, skeletal system defects, etc., as well as several autoimmune disorders. On the contrary, early triggering of cell suicide leads to degenerative disorders of the nervous and skeletal systems. (http://www.buzzle.com/articles/why-do-cells-commit-suicide.html)

Apoptosis and Cancer
Some viruses associated with cancers use tricks to prevent apoptosis of the cells they have transformed.
  • Several human papilloma viruses (HPV) have been implicated in causing cervical cancer. One of them produces a protein (E6) that binds and inactivates the apoptosis promoter p53.
  • Epstein-Barr Virus (EBV), the cause of mononucleosis and associated with some lymphomas
    • produces a protein similar to Bcl-2
    • produces another protein that causes the cell to increase its own production of Bcl-2. Both these actions make the cell more resistant to apoptosis (thus enabling a cancer cell to continue to proliferate).
Even cancer cells produced without the participation of viruses may have tricks to avoid apoptosis.
  • Some B-cell leukemias and lymphomas express high levels of Bcl-2, thus blocking apoptotic signals they may receive. The high levels result from a translocation of the BCL-2 gene into an enhancer region for antibody production.
  • Melanoma (the most dangerous type of skin cancer) cells avoid apoptosis by inhibiting the expression of the gene encoding Apaf-1.
  • Some cancer cells, especially lung and colon cancer cells, secrete elevated levels of a soluble "decoy" molecule that binds to FasL, plugging it up so it cannot bind Fas. Thus, cytotoxic T cells (CTL) cannot kill the cancer cells.
  • Other cancer cells express high levels of FasL, and can kill any cytotoxic T cells (CTL) that try to kill them because CTL also express Fas (but are protected from their own FasL) 
What makes a cell decide to commit suicide?
The balance between:
  • the withdrawal of positive signals; that is, signals needed for continued survival, and
  • the receipt of negative signals.

Withdrawal of positive signals

The continued survival of most cells requires that they receive continuous stimulation from other cells and, for many, continued adhesion to the surface on which they are growing. Some examples of positive signals:
  • growth factors for neurons
  • Interleukin-2 (IL-2), an essential factor for the mitosis of lymphocytes

Receipt of negative signals

  • increased levels of oxidants within the cell
  • damage to DNA by these oxidants or other agents like
  • accumulation of proteins that failed to fold properly into their proper tertiary structure
  • molecules that bind to specific receptors on the cell surface and signal the cell to begin the apoptosis program. These death activators include:
    • Tumor necrosis factor-alpha (TNF-α) that binds to the TNF receptor;
    • Lymphotoxin (also known as TNF-β) that also binds to the TNF receptor;
    • Fas ligand (FasL), a molecule that binds to a cell-surface receptor named Fas (also called CD95). 
    (http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html) 
Sydney Brenner, H. Robert Horvitz and John Sulston were awarded the Nobel Prize in Physiology or Medicine in 2002 "for their discoveries concerning genetic regulation of organ development and programmed cell death."
― Nobelprize.org

some blog post links related with multicellularity, nature of mitochondria and viruses, cancer cause and cure.
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