Cell death can occur through either uncontrolled necrosis or programmed apoptosis. Apoptosis involves the controlled destruction of cells through condensation of chromatin, fragmentation of DNA, and packaging of cell contents into vesicles for recycling. Apoptosis is triggered through either the intrinsic mitochondrial pathway or extrinsic death receptor pathway and plays an important role in development and tissue homeostasis. Cancer arises from uncontrolled cell growth caused by mutations to proto-oncogenes and tumor suppressor genes, which normally regulate the cell cycle and cell death. Mutagens like radiation and chemicals can cause these mutations, potentially leading to primary tumors and metastasis of secondary cancers.

1. Unit 1
APOPTOSIS

2. Cell Death
Cells have a limited proliferative capacity, after which division stops (Hayflick limit)
• Cells will enter a senescence (ageing) phase, leading to eventual cellular death
Cell death can either be uncontrolled (necrosis) or programmed (apoptosis)
APOPTOSIS
NECROSIS NORMAL
Swell
Burst Condense Fragment

3. Apoptosis versus Necrosis
Apoptosis (cell ‘suicide’)
• The controlled destruction of a cell
in response to molecular signals
• Cell shrinks, chromatin condenses
• Cell contents are packaged into
vesicles and recycled by the body
Necrosis (cell ‘homicide’)
• The premature death of a cell due
to injury or nutritional deprivation
• Cell becomes destabilised and lyses
• Cell contents are released into the
tissues, leading to inflammation

4. Apoptosis
Apoptosis is the process of programmed cell death (i.e. cell suicide)
• Cell contents are packaged and recycled for use by other cells
• Because contents are recycled, they do not induce an inflammatory response
Apoptosis may be triggered by either an intrinsic or extrinsic pathway, in which:
• The cell shrinks and develops membrane protrusions (blebbing)
• Chromatin clumps as DNA and proteins are cleaved by enzymes (caspases)
• Mitochondria breaks down (other organelles usually left intact for recycling)
• Cytoplasm is retained in apoptotic bodies (no resulting inflammatory reaction)

5. Intrinsic Pathway: Mitochondria
Apoptosis can be induced by intracellular signals
(e.g. DNA damage or oxidative stress responses)
• The mitochondrial membrane becomes permeable
• This releases apoptotic proteins (cytochrome c) and
also uncouples oxidative phosphorylation (no ATP)
• Apoptotic proteins activates caspases, which digest
cellular proteins within the cytoplasm and nucleus
• This results in apoptosis (cell shrinking, blebbing, etc.)
APOPTOSIS
apoptosome
caspase

6. Extrinsic Pathway: Death Receptor
Apoptosis can be induced by extracellular signals
(e.g. signaling molecules – such as cytokines)
• External ligands bind to a death receptor
• Death-inducing signaling complex (DISC) assembled
(via standard signal transduction mechanisms)
• Once assembled, DISC activates cellular caspases
• Caspases digest cytosolic and nuclear proteins
• This results in apoptosis (cell shrinking, blebbing, etc.)
APOPTOSIS
DISC
caspase
death
receptor
ligand

7. Role of Apoptosis
Apoptosis plays a vital role in organismal development and survival:
• It removes cells that are not needed or not developed (e.g. neural pruning)
• It recycles excess cells to reduce energy costs (e.g. immune cells post-infection)
Malfunctions to normal apoptotic processes can result in a variety of diseases:
• If apoptosis is inhibited, uncontrolled cell division may result in cancer
• If apoptosis is excessive, deterioration in tissue can lead to disorders such as
Parkinson’s disease or Alzheimer’s disease (both caused by loss of neural tissue)

8. Cancer
Cancer is caused by uncontrolled cell division and can occur in any tissue or organ
Tumors are the abnormal cellular growths formed as a result of cancer:
• Primary tumors remain in the originating tissue (i.e. benign growths)
• Secondary tumors have invaded neighboring tissues (i.e. malignant growths)
Metastasis is the spread of cancerous tissue from one location to another
• Secondary tumors are defined and treated according to the original cell type
➪ E.g. If breast cancer spreads to liver = secondary breast cancer of the liver
Mutagens, oncogenes and metastasis are involved in the development of primary and secondary tumors

9. Mutagens, oncogenes and metastasis are involved in the development of primary and secondary tumors
Mutagens
A mutagen is an agent that causes a change in the genetic material of an organism
• Mutagens that lead to the formation of cancer are further called carcinogens
Radiation Chemicals Infectious Agents
UV
(sunlight)
Bacteria
(Helicobacter)
X-rays
(medical)
Carcinogen
(cigarettes)
Processed
foods
Cleaning
products
Viruses
(HPV)

10. Mutagens, oncogenes and metastasis are involved in the development of primary and secondary tumors
Oncogenes
An oncogene is a gene that has the potential to cause cancer
Cancers may be caused by mutations to two basic classes of genes:
• Proto-oncogenes code for proteins that promote cell growth and proliferation
• Tumor suppressor genes code for proteins that repress cell cycle progression
When a proto-oncogene is mutated it becomes a cancer-causing oncogene
• Tumor suppressor genes are sometimes referred to as anti-oncogenes as they
normally function to prevent the occurrence of cancer (may promote apoptosis)

11. Cancer Summary
BRAKE
GAS
Proto-oncogenes promote cell growth – so mutations cause cancer (car crash!)
Anti-oncogenes promote apoptosis – so mutations can cause cancer (car crash!)
mutation
too much gas
mutation
cannot stop