Apoptosis
Dr Momna Hejmadi SHOULD I STAY OR SHOULD I DIE? DEATH-DEFYING CANCER CELLS
Death is a part of life
© stphillips
Cancer results from reduced cell death Kerr, Wylie and Currie (1972)
How cells die? Necrosis 1. Cell bursts open
© BrianAJackson
2. A typical cell
© David Marchal
Necrosis – Messy! Cell bursts open
A cell
No change in DNA Mitochondria swells up
Inflammatory Response
How cells die? Apoptosis 2. Genetically controlled programmed cell death
© University of Bath
Apoptosis Systematic dismantling of a cell
© defun
Apoptosis – Controlled! A cell
DNA neatly broken down No change in mitochondria
Apoptopic Bodies
Eaten up by a neighbouring cell or a cell from the immune system
Apoptosis is hard-wired into every cell Part of normal development 1. Duck Feet
© ChrisPole
2. Sculpting of fingers
© Cameramannz
Apoptosis triggered in normal cells when…. 1. Cell or DNA is damaged 2. Cell is stressed by other extreme physiological conditions 3. Apoptotic signals are sent by the surroundings or neighbouring cells
Apoptosis and disease Cancer cells switch OFF apoptosis
Apoptosis switched ON in Alzheimer’s disease
© Henrik5000
Cancer cells switch off apoptosis Stressed normal cell
Cancer cell
Active p53
Apoptosis
Inactive
NO
p53
Apoptosis
Treatment target Trigger apoptosis in cancer cells Drugs that activate receptors that switch ON apoptosis (Mapatumumab ®)
Cancer cell
TRAIL receptor
Apoptosis ON
Key Concepts from this session Cancers may arise due to insufficient or a lack of cell death Most common forms of cell death are a) Necrosis: Cells and mitochondria swell up, cell bursts, inflammation b) Apoptosis: Cell dismantles components, forms apoptotic bodies and no inflammatory response Apoptosis triggered by stress, damage or signalling molecules in normal cells. Triggering apoptosis is a useful strategy for treating some cancers
Distributed by UNIVERSITY OF BATH and FUTURELEARN under licence
Acknowledgements Academic content for ‘Inside Cancer’: © Dr Momna Hejmadi (Lead Educator), Dr Jim Caunt, Dr Andrew Chalmers, Professor Laurence Hurst, Dr Alex Jeffries, Dr Julien Licchesi, Dr Adele Murrell, Professor David Tosh, Dr Andrew Ward 2014 Production: © University of Bath 2014 Images: © iStockphoto.com/Henrik5000/05-03-10 © iStockphoto.com/stphillips/07-12-05 © iStockphoto.com/BrianAJackson/02-02-12 © iStockphoto.com/David Marchal/12-06-10
© iStockphoto.com/defun/12-11-13 © iStockphoto.com/ChrisPole/18-10-08 © iStockphoto.com/Cameramannz/16-09-10 © iStockphoto.com/Henrick5000/23-06-13
Death is a part of life
© stphillips
Cancer results from reduced cell death Kerr, Wylie and Currie (1972)
How cells die? Necrosis 1. Cell bursts open
© BrianAJackson
2. A typical cell
© David Marchal
Necrosis – Messy! Cell bursts open
A cell
No change in DNA Mitochondria swells up
Inflammatory Response
How cells die? Apoptosis 2. Genetically controlled programmed cell death
© University of Bath
Apoptosis Systematic dismantling of a cell
© defun
Apoptosis – Controlled! A cell
DNA neatly broken down No change in mitochondria
Apoptopic Bodies
Eaten up by a neighbouring cell or a cell from the immune system
Apoptosis is hard-wired into every cell Part of normal development 1. Duck Feet
© ChrisPole
2. Sculpting of fingers
© Cameramannz
Apoptosis triggered in normal cells when…. 1. Cell or DNA is damaged 2. Cell is stressed by other extreme physiological conditions 3. Apoptotic signals are sent by the surroundings or neighbouring cells
Apoptosis and disease Cancer cells switch OFF apoptosis
Apoptosis switched ON in Alzheimer’s disease
© Henrik5000
Cancer cells switch off apoptosis Stressed normal cell
Cancer cell
Active p53
Apoptosis
Inactive
NO
p53
Apoptosis
Treatment target Trigger apoptosis in cancer cells Drugs that activate receptors that switch ON apoptosis (Mapatumumab ®)
Cancer cell
TRAIL receptor
Apoptosis ON
Key Concepts from this session Cancers may arise due to insufficient or a lack of cell death Most common forms of cell death are a) Necrosis: Cells and mitochondria swell up, cell bursts, inflammation b) Apoptosis: Cell dismantles components, forms apoptotic bodies and no inflammatory response Apoptosis triggered by stress, damage or signalling molecules in normal cells. Triggering apoptosis is a useful strategy for treating some cancers
Distributed by UNIVERSITY OF BATH and FUTURELEARN under licence
Acknowledgements Academic content for ‘Inside Cancer’: © Dr Momna Hejmadi (Lead Educator), Dr Jim Caunt, Dr Andrew Chalmers, Professor Laurence Hurst, Dr Alex Jeffries, Dr Julien Licchesi, Dr Adele Murrell, Professor David Tosh, Dr Andrew Ward 2014 Production: © University of Bath 2014 Images: © iStockphoto.com/Henrik5000/05-03-10 © iStockphoto.com/stphillips/07-12-05 © iStockphoto.com/BrianAJackson/02-02-12 © iStockphoto.com/David Marchal/12-06-10
© iStockphoto.com/defun/12-11-13 © iStockphoto.com/ChrisPole/18-10-08 © iStockphoto.com/Cameramannz/16-09-10 © iStockphoto.com/Henrick5000/23-06-13
