Oxidative Stress in Cancer

Question 1

Reactive oxygen species examples

Answer 1

superoxide (O2*−)

hydroxyl (*OH)

ozone (O3)

singlet oxygen (1O2)

Question 2

Consequences of oxidative eustress

Answer 2

Adapted signalling (angiogenesis and proliferation) but no damage

Question 3

Consequences of oxidative stress

Answer 3

Inflammation, tumour growth and cell death

Question 4

G6PD in normal metabolism

Answer 4

Inhibited by NADPH

Question 5

Which transcription factor responds first to low ROS levels?

Answer 5

NRF2

Question 6

How does acute oxidative stress affect metabolism?

Answer 6

Reduced NADPH

Other pathways (kinases and phosphatases) stimulate G6PD

Question 7

Describe the role of oxidative stress in early stage of cancer

Answer 7

Reactive oxygen species are genotoxic

Question 8

Describe the role of oxidative stress in the preneoplastic proliferative stage of cancer

Answer 8

H202 signalling mediates cell proliferation

Question 9

Describe the role of oxidative stress in the invasive stage of cancer

Answer 9

H202 supports EMT and the pro-tumorigenic actions of macrophages

O2 and ONOO- used by immune cells to kill tumor cells

Question 10

Irreversible oxidation of _________ causes inhibition of _________ and activates ________ to promote cell survival.

Answer 10

cysteine

phosphatase

kinase

Question 11

Describe the role of oxidative stress in the metastatic stage of cancer

Answer 11

High O2 levels trigger apoptosis in certain types of tumor cells

Question 12

Nrf2 function

Answer 12

Binds to Keap1 and activates ubiquitin ligase transcription factor that degrades it

Question 13

Nrf2 half life

Answer 13

10-20 mins

Question 14

Which gene codes for Nrf2?

Answer 14

NFE2L2

Question 15

Keap1 mutations are usually…

Answer 15

missense.

Question 16

___________ metabolism is important in tumours with no Keap1 and high Nrf2.

Answer 16

Glutamine

Question 17

How does Nrf2 help cancer cells

Answer 17

Metabolic adaptation

Question 18

What do high levels of Nrf2 cause?

Answer 18

High levels of antioxidants at the expense of
contributing carbon to replenish the TCA cycle

Question 19

Glutaminase catalyzes the conversion of
glutamine to…

Answer 19

glutamate.

Question 20

What is the most abundant intracellular antioxidant?

Answer 20

Glutathione

Question 21

Glutaminase inhibitors effective?

Answer 21

No

Question 22

When Nrf2 is activated, __________ secretion is used for __________ synthesis and __________
import.

Answer 22

glutamate

glutathione

cystine

Question 23

Nrf2 activation in cancer cells creates sensitivity to which inhibitors?

Answer 23

HDAC

Question 24

What is the role of HDAC?

Answer 24

Chromatin remodelling