2) Given that E6 inactivates p53-dependent pathways, cervical cancer cells are p

Question

2) Given that E6 inactivates p53-dependent pathways, cervical cancer cells are particularly resistant to traditional treatments such as chemotherapy, the search is ongoing for new alternative therapeutics to be used in conjunction with current chemotherapeutic drugs. One such candidate is the plant flavonoid Luteolin. In 2014, Ham et al evaluate the effectiveness of Luteolin on sensitizing cervical cancer cells to apoptosis.

e) Authors sought to test for activation of apoptotic pathways resultant from Luteolin treatment. They decided to look at cleavage of caspases 9, 8, and 3 as shown in Figure 2, panel C.

i. Define caspases 9, 8, and 3 as initiators or executioner caspases.

Caspase 9 –

Caspase 8 –

Caspase 3 –

ii. What is the difference in caspases 9 and 8 with respect to apoptotic pathways. I.e. what information would the authors gain from looking at both of these?

iii. Which caspase, 8 or 9, is activated at lower doses of Luteolin?

iv. Based on your answer in question iii which statement best reflects the observations of the authors?

a) Luteolin only activates intrinsic apoptotic pathways.

b) Luteolin only activates extrinsic apoptotic pathways.

c) Luteolin activates the extrinsic pathway 1st, which in turn activates the intrinsic pathway.

d) Luteolin activates the intrinsic pathway 1st, which in turn activates the extrinsic pathway.

Figure 2: Ham et al Luteolin (uM) 5 10 20 Pro caspase-9 Cleavage caspase-9 Pro caspase-8 Cleavage caspase-8 Pro caspase-3 Cleavage caspase-5

Explanation / Answer

1. Caspase 9 and 8 are initiator caspase where as caspase 3 is executioner caspase.

ii. Caspase 9 is involved in intrinsic apoptotic pathway where as caspase 8 is involved in extrinsic pathway.

iii.Caspase 8 is activated at lower doses of luteolin.

iv.Luteolin activates the extrinsic pathway 1st, which in turn activates the intrinsic pathway.

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