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.

d. For each of the proteins indicate whether they showed increasing or decreasing levels with increased amounts of Luteolin.

p53

p21

Cyclin A

Cyclin E

i. Overall, the authors claimed that these results showed that cells were not proceeding into S-phase due to reactivation of p53-dependent pathways. How do these data support this claim?

Panel A: Figure 1: Ham et al E6 1.2 Panel B: 0.8 0.6 0.4 0.2 Luteolin (uM) 5 10 20 21 20 Luteolin (HM) Luteolin (LLM 5 10 20 Cyclin A Cyclin E

Explanation / Answer

D-

p53 - levels increase upon treatment with Luteolin

p21-levels increase upon treatment with Luteolin

Cyclin A- levels decrease upon treatment with Luteolin

Cyclin E- levels decrease upon treatment with Luteolin

I- As we can that the levels of p53 increases upon treatment with Luteolin. p21 is cyclin-dependent kinase(CDK) inhibitor which depends on the p53 on its expression. CDKs binds to the Cyclin E and A and leads to cell-cycle progression via S-phase. Thus we can say that it the level of p53 that leads to inhibition o cell-cycle progression when the cells were treated with luteolin.

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