Oxidative Stress in Cancer Flashcards
Reactive oxygen species examples
superoxide (O2*−)
hydroxyl (*OH)
ozone (O3)
singlet oxygen (1O2)
Consequences of oxidative eustress
Adapted signalling (angiogenesis and proliferation) but no damage
Consequences of oxidative stress
Inflammation, tumour growth and cell death
G6PD in normal metabolism
Inhibited by NADPH
Which transcription factor responds first to low ROS levels?
NRF2
How does acute oxidative stress affect metabolism?
Reduced NADPH
Other pathways (kinases and phosphatases) stimulate G6PD
Describe the role of oxidative stress in early stage of cancer
Reactive oxygen species are genotoxic
Describe the role of oxidative stress in the preneoplastic proliferative stage of cancer
H202 signalling mediates cell proliferation
Describe the role of oxidative stress in the invasive stage of cancer
H202 supports EMT and the pro-tumorigenic actions of macrophages
O2 and ONOO- used by immune cells to kill tumor cells
Irreversible oxidation of _________ causes inhibition of _________ and activates ________ to promote cell survival.
cysteine
phosphatase
kinase
Describe the role of oxidative stress in the metastatic stage of cancer
High O2 levels trigger apoptosis in certain types of tumor cells
Nrf2 function
Binds to Keap1 and activates ubiquitin ligase transcription factor that degrades it
Nrf2 half life
10-20 mins
Which gene codes for Nrf2?
NFE2L2
Keap1 mutations are usually…
missense.
___________ metabolism is important in tumours with no Keap1 and high Nrf2.
Glutamine
How does Nrf2 help cancer cells
Metabolic adaptation
What do high levels of Nrf2 cause?
High levels of antioxidants at the expense of
contributing carbon to replenish the TCA cycle
Glutaminase catalyzes the conversion of
glutamine to…
glutamate.
What is the most abundant intracellular antioxidant?
Glutathione
Glutaminase inhibitors effective?
No
When Nrf2 is activated, __________ secretion is used for __________ synthesis and __________
import.
glutamate
glutathione
cystine
Nrf2 activation in cancer cells creates sensitivity to which inhibitors?
HDAC
What is the role of HDAC?
Chromatin remodelling
